FHIT fragile histidine triad diadenosine triphosphatase [Homo sapiens (human)] - Gene

Summary

Official Symbol: FHITprovided by HGNC
Official Full Name: fragile histidine triad diadenosine triphosphataseprovided by HGNC
Primary source: HGNC:HGNC:3701
See related: Ensembl:ENSG00000189283 MIM:601153; AllianceGenome:HGNC:3701
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: FRA3B; AP3Aase
Summary: The protein encoded by this gene is a P1-P3-bis(5'-adenosyl) triphosphate hydrolase involved in purine metabolism. This gene encompasses the common fragile site FRA3B on chromosome 3, where carcinogen-induced damage can lead to translocations and aberrant transcripts. In fact, aberrant transcripts from this gene have been found in about half of all esophageal, stomach, and colon carcinomas. The encoded protein is also a tumor suppressor, as loss of its activity results in replication stress and DNA damage. [provided by RefSeq, Aug 2017]
Expression: Ubiquitous expression in gall bladder (RPKM 2.2), lymph node (RPKM 1.6) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3p14.2

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (59747277..61251452, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (59787636..61294609, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (59733003..61237126, complement)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Integrated analysis of FHIT gene alterations in cancer.
Title: Integrated analysis of FHIT gene alterations in cancer.
Expression of Tumor Suppressor FHIT Is Regulated by the LINC00173-SNAIL Axis in Human Lung Adenocarcinoma.
Title: Expression of Tumor Suppressor FHIT Is Regulated by the LINC00173-SNAIL Axis in Human Lung Adenocarcinoma.
The Rosetta Stone Hypothesis-Based Interaction of the Tumor Suppressor Proteins Nit1 and Fhit.
Title: The Rosetta Stone Hypothesis-Based Interaction of the Tumor Suppressor Proteins Nit1 and Fhit.
Investigation of the expression levels of CDH1, FHIT, PTEN, and TTPAL genes in colorectal tumors.
Title: Investigation of the expression levels of CDH1, FHIT, PTEN, and TTPAL genes in colorectal tumors.
System analysis of FHIT in LUAD and LUSC: The expression, prognosis, gene regulation network, and regulation targets.
Title: System analysis of FHIT in LUAD and LUSC: The expression, prognosis, gene regulation network, and regulation targets.
Germinal epimutation of Fragile Histidine Triad (FHIT) gene is associated with progression to acute and chronic adult T-cell leukemia diseases.
Title: Germinal epimutation of Fragile Histidine Triad (FHIT) gene is associated with progression to acute and chronic adult T-cell leukemia diseases.
rs73092672 allele T is significantly associated with the higher risk of breast cancer incidence.
Title: rs73092672 allele T is significantly associated with the higher risk of breast cancer incidence.
Locus-specific transcription silencing at the FHIT gene suppresses replication stress-induced copy number variant formation and associated replication delay.
Title: Locus-specific transcription silencing at the FHIT gene suppresses replication stress-induced copy number variant formation and associated replication delay.
Fhit induces the reciprocal suppressions between Lin28/Let-7 and miR-17/92miR.
Title: Fhit induces the reciprocal suppressions between Lin28/Let-7 and miR-17/92miR.
Relationship between Methylation of FHIT and CDH13 Gene Promoter Region and Liver Cancer.
Title: Relationship between Methylation of FHIT and CDH13 Gene Promoter Region and Liver Cancer.

Submit: New GeneRIF Correction See all GeneRIFs (270)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2018-10-24) ClinGen Genome Curation PagePubMed Haploinsufficency No evidence available (Last evaluated 2018-10-24) ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
A genome-wide association study (GWAS) for bronchopulmonary dysplasia. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide association study provides evidence for association of chromosome 8p23 (MYP10) and 10q21.1 (MYP15) with high myopia in the French Population. EBI GWAS Catalog EBI GWAS CatalogPubMed
Gene-age interactions in blood pressure regulation: a large-scale investigation with the CHARGE, Global BPgen, and ICBP Consortia. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic variants associated with breast size also influence breast cancer risk. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome wide study of maternal and parent-of-origin effects on the etiology of orofacial clefts. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association studies of pit-and-fissure- and smooth-surface caries in permanent dentition. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of d-amphetamine response in healthy volunteers identifies putative associations, including cadherin 13 (CDH13). EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of maternal and inherited loci for conotruncal heart defects. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of recurrent early-onset major depressive disorder. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide joint SNP and CNV analysis of aortic root diameter in African Americans: the HyperGEN study. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide mapping for clinically relevant predictors of lamotrigine- and phenytoin-induced hypersensitivity reactions. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide pharmacogenomic study of citalopram-induced side effects in STAR*D. EBI GWAS Catalog EBI GWAS CatalogPubMed
Variants in several genomic regions associated with asperger disorder. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	HIV-1 Tat-fused fragile histidine triad (FHIT) can robustly inhibit growth and induce apoptosis of human hepatocellular carcinoma cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-82698 (e-PCR)
- UniSTS:102411

STS-N70372 (e-PCR)
- UniSTS:79378

RH16423 (e-PCR)
- UniSTS:49696

G59345 (e-PCR)
- UniSTS:136510

RH123369 (e-PCR)
- UniSTS:135745

SHGC-33999 (e-PCR)
- UniSTS:11338

SHGC-145137 (e-PCR)
- UniSTS:174412

D3S1300 (e-PCR), detects polymorphism
- UniSTS:6989

SHGC-78605 (e-PCR)
- UniSTS:101710

RH36473 (e-PCR)
- UniSTS:57692

D3S1480 (e-PCR)
- UniSTS:148322

D3S1481 (e-PCR)
- UniSTS:148323

D3S3356 (e-PCR)
- UniSTS:69994

SHGC-77051 (e-PCR)
- UniSTS:9066

D3S2757 (e-PCR)
- UniSTS:150385

D3S3424 (e-PCR)
- UniSTS:18063

SHGC-13229 (e-PCR)
- UniSTS:14227

G69476 (e-PCR)
- UniSTS:229525

D17S610 (e-PCR)
- UniSTS:46230

SHGC-77059 (e-PCR)
- UniSTS:5278

D3S3155 (e-PCR)
- UniSTS:153246

G59179 (e-PCR)
- UniSTS:136353

D3S2977 (e-PCR)
- UniSTS:32162

SHGC-83813 (e-PCR)
- UniSTS:101794

D3S1234 (e-PCR), detects polymorphism
- UniSTS:33703

AFMA285ZB5 (e-PCR)
- UniSTS:45993

STS-T91564 (e-PCR)
- UniSTS:10414

D3S3367 (e-PCR)
- UniSTS:60846

SHGC-58369 (e-PCR)
- UniSTS:71857

SHGC-80947 (e-PCR)
- UniSTS:102580

SHGC-111527 (e-PCR)
- UniSTS:168378

D3S3378 (e-PCR)
- UniSTS:19646

D3S3136 (e-PCR)
- UniSTS:26056

RH46243 (e-PCR)
- UniSTS:68316

STS-AA004994 (e-PCR)
- UniSTS:43228

RH119292 (e-PCR)
- UniSTS:133854

D3S1300 (e-PCR), detects polymorphism
- UniSTS:13792

D3S2984 (e-PCR)
- UniSTS:5348

G49403 (e-PCR)
- UniSTS:140774

SHGC-80066 (e-PCR)
- UniSTS:102124

L18045 (e-PCR)
- UniSTS:19693

G49406 (e-PCR)
- UniSTS:140787

SHGC-86352 (e-PCR)
- UniSTS:183801

D3S3631 (e-PCR), detects polymorphism
- UniSTS:52732

SHGC-77038 (e-PCR)
- UniSTS:68606

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables adenosine 5'-monophosphoramidase activity	IDA Inferred from Direct Assay more info	PubMed
enables adenylylsulfatase activity	IDA Inferred from Direct Assay more info	PubMed
enables adenylylsulfate-ammonia adenylyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables bis(5'-adenosyl)-triphosphatase activity	IBA Inferred from Biological aspect of Ancestor more info
enables bis(5'-adenosyl)-triphosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables nucleotide binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin protein ligase binding	IBA Inferred from Biological aspect of Ancestor more info
enables ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in diadenosine triphosphate catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in diadenosine triphosphate catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in intrinsic apoptotic signaling pathway by p53 class mediator	IBA Inferred from Biological aspect of Ancestor more info
involved_in intrinsic apoptotic signaling pathway by p53 class mediator	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of proteasomal ubiquitin-dependent protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of proteasomal ubiquitin-dependent protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in purine nucleotide metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in purine nucleotide metabolic process	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in fibrillar center	IDA Inferred from Direct Assay more info
located_in mitochondrion	HTP more info	PubMed
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: bis(5'-adenosyl)-triphosphatase

Names: AP3A hydrolase; adenosine 5'-monophosphoramidase FHIT; adenylylsulfatase; adenylylsulfate-ammonia adenylyltransferase; diadenosine 5',5'''-P1,P3-triphosphate hydrolase; dinucleosidetriphosphatase

NP_001159715.1

EC 2.7.7.51

EC 3.6.1.29

EC 3.6.2.1

NP_001307828.1

EC 2.7.7.51

EC 3.6.1.29

EC 3.6.2.1

NP_001307829.1

EC 2.7.7.51

EC 3.6.1.29

EC 3.6.2.1

NP_001307830.1

EC 2.7.7.51

EC 3.6.1.29

EC 3.6.2.1

NP_001341518.1

EC 2.7.7.51

EC 3.6.1.29

EC 3.6.2.1

NP_001341519.1

EC 2.7.7.51

EC 3.6.1.29

EC 3.6.2.1

NP_002003.1

EC 2.7.7.51

EC 3.6.1.29

EC 3.6.2.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007551.2 RefSeqGene

Range

5008..1509183

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001166243.3 → NP_001159715.1 bis(5'-adenosyl)-triphosphatase isoform 1

See identical proteins and their annotated locations for NP_001159715.1

Status: REVIEWED

Description

Transcript Variant: This variant (2), as well as variants 1, 3, and 4, encodes isoform 1.

Source sequence(s)

AC132808, BC032336, DB477833

Consensus CDS

CCDS2894.1

UniProtKB/Swiss-Prot

A2IAS9, A2IAT0, A2IAT6, A8K1A9, P49789, Q45QG9, Q6IU12

Related

ENSP00000417557.1, ENST00000476844.5

Conserved Domains (1) summary

cd01275
Location:5 → 124

FHIT; FHIT (fragile histidine family): FHIT proteins, related to the HIT family carry a motif HxHxH/Qxx (x, is a hydrophobic amino acid), On the basis of sequence, substrate specificity, structure, evolution and mechanism, HIT proteins are classified into ...
NM_001320899.2 → NP_001307828.1 bis(5'-adenosyl)-triphosphatase isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (3), as well as variants 1, 2, and 4, encodes isoform 1.

Source sequence(s)

AC132808, AK289824, DB477833

Consensus CDS

CCDS2894.1

UniProtKB/Swiss-Prot

A2IAS9, A2IAT0, A2IAT6, A8K1A9, P49789, Q45QG9, Q6IU12

Related

ENSP00000417480.1, ENST00000468189.5

Conserved Domains (1) summary

cd01275
Location:5 → 124

FHIT; FHIT (fragile histidine family): FHIT proteins, related to the HIT family carry a motif HxHxH/Qxx (x, is a hydrophobic amino acid), On the basis of sequence, substrate specificity, structure, evolution and mechanism, HIT proteins are classified into ...
NM_001320900.2 → NP_001307829.1 bis(5'-adenosyl)-triphosphatase isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (4), as well as variants 1-3, encodes isoform 1.

Source sequence(s)

AC096917, AC097357, AC098480, AC099536, AC099780, AC132808, AC138071

Consensus CDS

CCDS2894.1

UniProtKB/Swiss-Prot

A2IAS9, A2IAT0, A2IAT6, A8K1A9, P49789, Q45QG9, Q6IU12

Conserved Domains (1) summary

cd01275
Location:5 → 124

FHIT; FHIT (fragile histidine family): FHIT proteins, related to the HIT family carry a motif HxHxH/Qxx (x, is a hydrophobic amino acid), On the basis of sequence, substrate specificity, structure, evolution and mechanism, HIT proteins are classified into ...
NM_001320901.2 → NP_001307830.1 bis(5'-adenosyl)-triphosphatase isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (5) encodes a protein with a shorter N-terminus than isoform 1.

Source sequence(s)

AC132808, BE246370, DB131595

Conserved Domains (1) summary

cl00228
Location:4 → 68

HIT_like; HIT family: HIT (Histidine triad) proteins, named for a motif related to the sequence HxHxH/Qxx (x, a hydrophobic amino acid), are a superfamily of nucleotide hydrolases and transferases, which act on the alpha-phosphate of ribonucleotides. On the basis ...
NM_001354589.2 → NP_001341518.1 bis(5'-adenosyl)-triphosphatase isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (7), as well as variant 8, encodes isoform 3.

Source sequence(s)

AC096917, AC097357, AC099536, AC099780, AC132808, AC138071

Conserved Domains (1) summary

cl00228
Location:5 → 92

HIT_like; HIT family: HIT (Histidine triad) proteins, named for a motif related to the sequence HxHxH/Qxx (x, a hydrophobic amino acid), are a superfamily of nucleotide hydrolases and transferases, which act on the alpha-phosphate of ribonucleotides. On the basis ...
NM_001354590.2 → NP_001341519.1 bis(5'-adenosyl)-triphosphatase isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (8), as well as variant 7, encodes isoform 3.

Source sequence(s)

AC096917, AC097357, AC099536, AC099780, AC132808, AC138071

Conserved Domains (1) summary

cl00228
Location:5 → 92

HIT_like; HIT family: HIT (Histidine triad) proteins, named for a motif related to the sequence HxHxH/Qxx (x, a hydrophobic amino acid), are a superfamily of nucleotide hydrolases and transferases, which act on the alpha-phosphate of ribonucleotides. On the basis ...
NM_002012.4 → NP_002003.1 bis(5'-adenosyl)-triphosphatase isoform 1

See identical proteins and their annotated locations for NP_002003.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1). Variants 1-4 all encode the same isoform (1).

Source sequence(s)

AC132808, DB477833, U46922

Consensus CDS

CCDS2894.1

UniProtKB/Swiss-Prot

A2IAS9, A2IAT0, A2IAT6, A8K1A9, P49789, Q45QG9, Q6IU12

Related

ENSP00000418582.1, ENST00000492590.6

Conserved Domains (1) summary

cd01275
Location:5 → 124

FHIT; FHIT (fragile histidine family): FHIT proteins, related to the HIT family carry a motif HxHxH/Qxx (x, is a hydrophobic amino acid), On the basis of sequence, substrate specificity, structure, evolution and mechanism, HIT proteins are classified into ...

RNA

NR_135491.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (6) is represented as non-coding because the predicted ORF does not meet RefSeq quality criteria.

Source sequence(s)

AC099780, AC132808, AK127931, BE246370
NR_148921.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC096917, AC097357, AC104164, AC138071
NR_148922.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC096917, AC097357, AC138071