RDH5

retinol dehydrogenase 5, the group of Short chain dehydrogenase/reductase superfamily

Basic information

Region (hg38): 12:55720367-55724705

Previous symbols: [ "RDH1" ]

Links

ENSG00000135437 ∙ NCBI:5959 ∙ OMIM:601617 ∙ HGNC:9940 ∙ Uniprot:Q92781 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• fundus albipunctatus (Strong), mode of inheritance: AR
• fundus albipunctatus (Supportive), mode of inheritance: AD
• fundus albipunctatus (Definitive), mode of inheritance: Semidominant
• RDH5-related retinopathy (Definitive), mode of inheritance: AR
• fundus albipunctatus (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Fundus albipunctatus	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	10617778; 10369264; 11153648; 11812441; 16637847; 20829743; 21529959; 22669287; 22736946; 22815624

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RDH5 gene.

• not provided (29 variants)
• Pigmentary retinal dystrophy (10 variants)
• Fundus albipunctatus, autosomal recessive (4 variants)
• Retinal dystrophy (3 variants)
• Retinitis punctata albescens (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RDH5 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	48	3	56
missense	5	8	119	6		138
nonsense	9	2				11
start loss						0
frameshift	15	4	1			20
inframe indel	1		2			3
splice donor/acceptor (+/-2bp)	1	1				2
splice region			3	8		11
non coding			6	14	8	28
Total	31	15	133	68	11

Highest pathogenic variant AF is 0.0000394

Variants in RDH5

This is a list of pathogenic ClinVar variants found in the RDH5 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-55720397-C-T		Pigmentary retinal dystrophy	Benign (May 24, 2021)
12-55720398-G-A		Pigmentary retinal dystrophy	Uncertain significance (Jan 13, 2018)
12-55720427-G-A		Pigmentary retinal dystrophy	Uncertain significance (Jan 12, 2018)
12-55720430-G-A		Pigmentary retinal dystrophy	Likely benign (Jan 13, 2018)
12-55720518-G-GT		Pigmentary retinal dystrophy	Likely pathogenic (May 05, 2018)
12-55720985-G-C			Benign (Nov 05, 2018)
12-55721144-C-T		not specified • Pigmentary retinal dystrophy	Likely benign (Jan 12, 2018)
12-55721190-G-A			Pathogenic (Mar 12, 2024)
12-55721192-T-C		Retinal dystrophy	Uncertain significance (Apr 23, 2017)
12-55721197-C-CT			Pathogenic (Aug 01, 2022)
12-55721211-C-G			Likely benign (Apr 24, 2021)
12-55721215-C-T			Uncertain significance (Aug 07, 2022)
12-55721223-A-C			Likely benign (Jan 30, 2021)
12-55721226-G-A			Likely benign (Jul 23, 2024)
12-55721227-C-T			Likely benign (Dec 15, 2021)
12-55721228-T-C		Retinal dystrophy	Uncertain significance (Jul 05, 2022)
12-55721236-C-A			Uncertain significance (Dec 31, 2020)
12-55721238-C-T			Uncertain significance (Mar 01, 2022)
12-55721238-CAG-C		Pigmentary retinal dystrophy	Likely pathogenic (May 01, 2024)
12-55721240-G-A		Inborn genetic diseases	Uncertain significance (Jan 10, 2023)
12-55721245-C-G			Uncertain significance (Apr 14, 2021)
12-55721246-G-A			Uncertain significance (Oct 18, 2022)
12-55721248-C-T			Pathogenic (May 06, 2022)
12-55721249-A-G			Uncertain significance (May 28, 2022)
12-55721251-AGCCT-A		Pigmentary retinal dystrophy	Pathogenic (Jan 30, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RDH5	protein_coding	protein_coding	ENST00000257895	4	4339

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.87e-11	0.0432	125643	0	105	125748	0.000418

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.394	171	186	0.919	0.0000112	2004
Missense in Polyphen		49	55.098	0.88933		588
Synonymous	0.101	78	79.1	0.986	0.00000425	728
Loss of Function	-0.195	15	14.2	1.06	0.00000112	107

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000826	0.000825
Ashkenazi Jewish	0.00129	0.00129
East Asian	0.000653	0.000653
Finnish	0.00	0.00
European (Non-Finnish)	0.000442	0.000440
Middle Eastern	0.000653	0.000653
South Asian	0.000131	0.000131
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Stereospecific 11-cis retinol dehydrogenase, which catalyzes the final step in the biosynthesis of 11-cis retinaldehyde, the universal chromophore of visual pigments. Also able to oxidize 9-cis-retinol and 13-cis-retinol, but not all- trans-retinol. Active in the presence of NAD as cofactor but not in the presence of NADP. {ECO:0000269|PubMed:10588954, ECO:0000269|PubMed:9115228}.
• Pathway: Retinol metabolism - Homo sapiens (human);Vitamin A and Carotenoid Metabolism;Signaling by GPCR;Signal Transduction;RA biosynthesis pathway;The canonical retinoid cycle in rods (twilight vision);Visual signal transduction: Rods;Signaling by Retinoic Acid;Signaling by Nuclear Receptors;G alpha (i) signalling events;Visual phototransduction;the visual cycle I (vertebrates);GPCR downstream signalling;Visual signal transduction: Cones (Consensus)

Recessive Scores

• pRec: 0.218

Intolerance Scores

• loftool: 0.305
• rvis_EVS: 0.08
• rvis_percentile_EVS: 60.31

Haploinsufficiency Scores

• pHI: 0.410
• hipred: N
• hipred_score: 0.282
• ghis: 0.485

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.904

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rdh5
• Phenotype: vision/eye phenotype

Gene ontology

• Biological process: retinoid metabolic process;visual perception;retinol metabolic process;response to stimulus;oxidation-reduction process
• Cellular component: endoplasmic reticulum lumen;endoplasmic reticulum membrane;cell body
• Molecular function: retinol dehydrogenase activity