Table. [Genes with Highly Homologous Gene Family Members or a Pseudogene(s)]. - GeneReviews®

Table.

Genes with Highly Homologous Gene Family Members or a Pseudogene(s)

Gene ¹	Homologous Genes and Pseudogenes	Disorder Caused by Pathogenic Variants in this Gene ²	Proportion of Affected Individuals with Pathogenic Variants in This Gene
ABCC6 ³	ABCC6P1 ABCC6P2	Pseudoxanthoma elasticum	100%
ABCD1	≥5 pseudogenes	X-linked adrenoleukodystrophy	100%
ACTB	≥18 pseudogenes	Baraitser-Winter syndrome cerebrofrontofacial syndrome	>60%
AK2	AK2P1 AK2P2	Reticular dysgenesis (See X-Linked Severe Combined Immunodeficiency.)	100%
ALG1	≥8 pseudogenes	ALG1-CDG (CDG-type Ik) (See Congenital Disorders of N-linked Glycosylation & Multiple Pathway Overview.)	100%
ANKRD11	LOC100419906 LOC100287912	KBG syndrome	100%
ASL	ASLP1	Argininosuccinate lyase deficiency	100%
ASS1	≥14 pseudogenes	Citrullinemia type I	100%
BANF1	≥5 pseudogenes	Nestor-Guillermo progeria syndrome (OMIM 614008)	100%
BMPR1A	BMPR1APS1 BMPR1APS2	Juvenile polyposis syndrome	20%-25%
C4A	CYP21A	C4A deficiency (OMIM 614380)	100%
C4B	CYP21A	C4B deficiency (OMIM 614379)	100%
CA5A	CA5AP1	Carbonic anhydrase VA deficiency	100%
CDC42	≥9 pseudogenes	Takenouchi-Kosaki syndrome (OMIM 616737)	2 individuals
CEL	CELP	Diabetes-pancreatic exocrine dysfunction syndrome (OMIM 609812)	2 families
CFH	CFHR1 CFHR2 CFHR3 CFHR4	Genetic atypical hemolytic-uremic syndrome	~50%
CFH	CFHR5	C3 glomerulopathy	~10%
CFTR ⁴	CFTRP1 CFTRP3	Cystic fibrosis & congenital absence of the vas deferens	100%
CHEK2	≥5 pseudogenes	Breast cancer susceptibility (OMIM 114480)	<5%
CHEK2	≥5 pseudogenes	Prostate cancer susceptibility (OMIM 176807)	<5%
CORO1A	LOC606724	Immunodeficiency 8 (OMIM 615401)	100%
CRIPTO (TDGF1)	≥7 pseudogenes	Holoprosencephaly	2 individuals
CRYBB2 ⁵	CRYBB2P1	Cataract 3, multiple types (OMIM 601547)	100%
CYCS	≥37 pseudogenes	Thrombocytopenia, AD, nonsyndromic, type IV (OMIM 612004)	100%
CYP21A2 ⁶	CYP21A1P	21-hydroxylase-deficient congenital adrenal hyperplasia	100%
DCLRE1C ⁷	DCLRE1CP1	Omenn syndrome (OMIM 603554)	>70 individuals
DCLRE1C ⁷	DCLRE1CP1	SCID Athabaskan (OMIM 602450)	100%
DDX11	≥6 pseudogenes	Warsaw breakage syndrome	100%
DHFR	≥4 pseudogenes	Megaloblastic anemia due to dihydrofolate reductase deficiency (OMIM 613839)	100%
DIS3L2	DIS3L2P1	Perlman syndrome (OMIM 267000)	100%
DPY19L2	≥5 pseudogenes	Globozoospermia, spermatogenic failure (OMIM 613958)	100%
EIF4E	≥5 pseudogenes	Autism (OMIM 615091)	3 families
FANCD2	FANCD2P1	Fanconi anemia	~3%
FLNC	LOC392787	Hypertrophic cardiomyopathy (OMIM 102565)	8 families
		Restrictive cardiomyopathy (OMIM 617047)	2 families
		Distal ABD-filaminopathy	100%
		Myofibrillar myopathy (OMIM 609524)	3%
GBA1 (GBA) ⁸	GBA1LP (GBAP)	Gaucher disease	100%
GCSH	≥8 pseudogenes	Nonketotic hyperglycinemia	<1%
GJA1	GJA6P GJA1P1	Oculodentodigital dysplasia (OMIM 164200)	100%
		Craniometaphyseal dysplasia, AR (OMIM 218400)	100%
		Palmoplantar keratoderma and congenital alopecia type 1 (OMIM 104100)	100%
		Hypoplastic left heart syndrome (OMIM 241550)	8 individuals
GK	GK3P GK6P GK4P	Glycerol kinase deficiency (OMIM 307030)	100%
GLDC ⁹	GLDCP1	Nonketotic hyperglycinemia	70%-75%
GLUD1	≥6 pseudogenes	Familial hyperinsulinism	5%
GNAQ	GNAQP1	Sturge-Weber syndrome (OMIM 185300)	88%
HBA1 ¹⁰ HBA2	HBAP1 HBZP	Alpha-thalassemia	100%
HBB	HBBP1	Sickle cell disease	100%
HBB	HBBP1	Beta-thalassemia	100%
HCN4	≥2 pseudogenes	Brugada syndrome	<1%
HPS1 ¹¹	LOC100500719	Hermansky-Pudlak syndrome	75% of Puerto Ricans; 44% of individuals not of Puerto Rican descent
HSPD1	≥23 pseudogenes	Hypomyelinating leukodystrophy (OMIM 612233)	2 individuals
HSPD1	≥23 pseudogenes	Hereditary spastic paraplegia (OMIM 605280)	1 family
HYDIN	HYDIN2	Primary ciliary dyskinesia	Founder variant in Faroe Islands; 1 additional family
IDS ¹²	IDSP1	Mucopolysaccharidosis type II	100%
IFT122	LOC653712	Cranioectodermal dysplasia	~10%
IKBKG	IKBKGP1	Incontinentia pigmenti	~75%
KAL1	KALP	Kallmann syndrome (See Isolated Gonadotropin-Releasing Hormone Deficiency.)	5%-10%
KRT16	≥5 pseudogenes	Pachyonychia congenita	29%
KRT16	≥5 pseudogenes	Palmoplantar keratoderma, nonepidermolytic (focal) (OMIM 613000)	≥5 families
KRT6A	≥4 pseudogenes	Pachyonychia congenita	42%
KRT86	KRT87P KRT88P	Monilethrix (OMIM 158000)	≥4 families
LEFTY2	LEFTY3	Left-right axis malformations (OMIM 601877)	2 individuals
MATR3	LOC100499497 LOC100499496 LOC401957	Amyotrophic lateral sclerosis type 21 (OMIM 606070)	5 families
NCF1	NCF1B NCF1C	Chronic granulomatous disease	20%
NF1	≥11 pseudogenes	Neurofibromatosis type 1	100%
NLRP7	LOC100421039	Recurrent hydatidiform mole (OMIM 231090)	~75%
NOTCH2	NOTCH2P1	Alagille syndrome	1%-2%
NOTCH2	NOTCH2P1	Hajdu-Cheney syndrome (OMIM 102500)	100%
OCLN	LOC647859	Band-like calcification with simplified gyration and polymicrogyria (OMIM 251290)	100%
OPHN1	ARHGAP42P3	X-linked intellectual disability with cerebellar hypoplasia and distinctive facial appearance (OMIM 300486)	8 families
OTOA	LOC653786	Deafness, AR, type 22 (OMIM 607038)	100%
PHKA1	PHKA1P1	Phosphorylase kinase deficiency	~17%
PIK3CA	LOC100422375	PIK3CA-related segmental overgrowth	100%
PKD1	≥7 pseudogenes	Polycystic kidney disease, AD	85%
PLEKHM1	PLEKHM1P1	Osteopetrosis, AR type 6 (OMIM 611497)	100%
PMM2	PMM2P1	PMM2-CDG (CDG-Ia)	100%
PMS2 ¹³	≥14 pseudogenes	Lynch syndrome	<5%
PRODH	LOC440792	Hyperprolinemia, type 1 (OMIM 239500)	100%
PROS1	PROS2P	Thrombophilia due to protein S deficiency (OMIM 176880)	100%
PRSS1 ¹⁴	PRSS3P2 PRSS3P1	Hereditary pancreatitis (See Pancreatitis Overview.)	60%-100%
PTEN	PTENP1	PTEN hamartoma tumor syndrome	100%
RBM8A	RBM8B	Thrombocytopenia absent radius syndrome	100%
RPS17	≥16 pseudogenes	Diamond-Blackfan anemia	~1%
RPS19	≥7 pseudogenes	Diamond-Blackfan anemia	25%
SALL1	SALL1P1	Townes-Brocks syndrome	75%
SBDS ¹⁵	SBDSP	Shwachman-Diamond syndrome	100%
SDHA	≥4 pseudogenes	Hereditary paraganglioma-pheochromocytoma syndromes	1%-3%
SDHC	≥5 pseudogenes	Hereditary paraganglioma-pheochromocytoma syndromes	4%-8%
SDHD	≥7 pseudogenes	Hereditary paraganglioma-pheochromocytoma syndromes	~30%
SFTPA2	SFTPA3P	Idiopathic pulmonary fibrosis (See Familial Pulmonary Fibrosis.)	2 families
SLC25A15	≥5 pseudogenes	Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome	100%
SLC6A8	SCL6A10P SCL6A10PB	Creatine deficiency syndromes	56%
SMAD4 ¹⁶	≥1 pseudogene (not named)	Juvenile polyposis syndrome ± Hereditary hemorrhagic telangiectasia	20%
SMN1 SMN2	SMNP LOC100132090	Spinal muscular atrophy	100%
STRC ¹⁷	STRCP1	STRC-related autosomal recessive hearing loss	6%-11%
TARDBP	LOC643387 TARDBPP1 TARDBPP2	TARDBP-related amyotrophic lateral sclerosis-frontotemporal dementia	100%
TBX20	LOC100418730	ASD type 4 (OMIM 611363)	3 families
TIMM8A	TIMM8AP1	Deafness-dystonia-optic neuronopathy syndrome	13 individuals
TMEM231	LOC100420067	Joubert syndrome	2 families & 2 individuals
TNXB	TNXA	TNXB-related classic-like Ehlers-Danlos syndrome	100%
TPI1	≥4 pseudogenes	Hemolytic anemia due to triosephosphate isomerase deficiency (OMIM 615512)	100%
TUBA1A	TUBA3GP LOC100129818	Lissencephaly and other complex cortical malformations (See Tubulinopathies Overview.)	37% of classic lissencephaly
TUBB2B	TUBB8P4 TUBB4BP2 TUBB2BP1	Polymicrogyria-like cortical dysplasia (See Tubulinopathies Overview.)	87.5%
TYR	TYRL	Oculocutaneous albinism type I (OMIM 203100, 606952)	100%
UBE3A	UBE3AP2 UBE3AP1	Angelman syndrome	~11%
VWF	VWFP1	von Willebrand disease	100%

: AD = autosomal dominant; AR = autosomal recessive; ASD = atrial septal defect
1.: Included in this table are genes that have: (1) one or more identified pseudogenes; and (2) pathogenic variants identified in more than one individual or family. Genes from the same gene family are listed together.
2.: For more information see hyperlinked GeneReview. An OMIM phenotype entry is provided if a GeneReview is not available.
3.: Two pseudogenes are almost identical to ABCC6 [Pfendner et al 2008].
4.: Duplication of exon 10 [Rozmahel et al 1997]
5.: Gene conversion between CRYBB2 and CRYBB2P1 was reported by Vanita et al [2001].
6.: Testing the proband and parents may be required to clarify results [Hong et al 2015].
7.: The most common DCLRE1C pathogenic variant is a deletion resulting from homologous recombination of DCLRE1C and the pseudogene [Pannicke et al 2010].
8.: GBA1LP is 96% homologous to GBA1 [Basgalupp et al 2018].
9.: The processed pseudogene has 97.5% homology to the coding sequence of GLDC [Takayanagi et al 2000].
10.: HBA1 and HBA2 have identical coding regions. This gene family also includes the embryonically expressed HBZ, HBD, and HBQ1.
11.: The pseudogene has 95% homology to HPS1; exon 6 is identical [Huizing et al 2000].
12.: 9% of pathogenic variants are complex rearrangements with the pseudogene. The pseudogene is 96% homologous to IDS [Bondeson et al 1995].
13.: Ongoing evolutionary sequence exchange between PMS2 and one pseudogene (PMS2CL) has led to unreliable reference sequences and false positive and false negative results on sequencing [Hayward et al 2007] (see also Vaughn et al [2011]).
14.: Regardless of the sequencing method employed, primers must be carefully chosen and validated to amplify the fragment for the correct gene and transcript. Thus, a multistep method is required to verify the presence of a pathogenic variant in PRSS1 [Masson et al 2008].
15.: Interpretations may be difficult as the extent of variation in SBDSP is not known. SBDSP is 97% homologous to SBDS.
16.: The presence of a processed pseudogene led to false positive MLPA results in some individuals [Millson et al 2015].
17.: STRCP1 is 99.6% homologous to STRC [Vona et al 2015].

From: Resources for Genetics Professionals — Genes with Highly Homologous Gene Family Members or a Pseudogene(s)

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Adam MP, Feldman J, Mirzaa GM, et al., editors.

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