RDH8

protein-coding

retinol dehydrogenase 8, the group of Short chain dehydrogenase/reductase superfamily

Gene summary

This gene encodes a member of the short-chain dehydrogenase/reductase family. The encoded protein catalyzes the reduction of all-trans-retinal to all-trans-retinol, the first reaction step of the rhodopsin regeneration pathway. This enzymatic reaction is the rate-limiting step in the visual cycle. [provided by RefSeq, Feb 2014]

MANE transcript

NM_015725.4

Inheritance

—

ClinVar variants

P:2U:17B:6

Top phenotype

Stargardt disease 5

gnomAD constraint

pLI —, LoF o/e 0.58

Max pathogenic AF

—

Genomic locus

chr19:10,013,249-10,022,279

External References & Databases

Ensembl (ENSG00000080511)

Transcript & Mutation Effects

hg38 • Region Span ~9.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RDH8 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 16

not providedTotal: 5

Stargardt disease 5Total: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015725.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar		2 clinvar	3
missense			13 clinvar	2 clinvar	2 clinvar	17
nonsense			1 clinvar			1
start loss						0
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)	1 clinvar		2 clinvar			3
Total	1	1	17	2	4	25

Highest pathogenic variant AF is 0.000013014604

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015725.4	RefSeq	NP_056540.3	6	MANE Select
ENST00000591589.3	Ensembl	ENSP00000466058.2	6	MANE Select
ENST00000587782.1	Ensembl	ENSP00000465773.1	3	Standard
ENST00000651512.1	Ensembl	ENSP00000498711.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Retinol metabolism - Homo sapiens (human)
Vitamin A Deficiency
Retinol Metabolism
Vitamin A and Carotenoid Metabolism
Signaling by GPCR

Biological Process

steroid biosynthetic process
estrogen biosynthetic process
visual perception
retinol metabolic process
response to stimulus

Molecular Function

estradiol 17-beta-dehydrogenase activity
retinol dehydrogenase activity
NADP-retinol dehydrogenase activity

Cellular Component

cytoplasm
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000591589
Coding exons: 6
Length: 9031
Individuals with no LoFs: 125725
Homozygous LoFs: 0
Heterozygous LoFs: 23
Defined: 125748
p: 0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.258	201	212	0.950	0.0000139	2104
Missense (PolyPhen)		71	78.63	0.90296		844
Synonymous	0.126	89	90.5	0.983	0.00000608	725
Loss of Function	1.26	6	10.4	0.578	4.40e-7	125

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.00027	0.00026	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Retinol dehydrogenase with a clear preference for NADP. Converts all-trans-retinal to all-trans-retinol. May play a role in the regeneration of visual pigment at high light intensity (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.136

Intolerance Scores

RVIS EVS: 0.69
RVIS percentile EVS: 85.18

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.0936

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium