RDH12

retinol dehydrogenase 12, the group of Short chain dehydrogenase/reductase superfamily

Basic information

Region (hg38): 14:67701885-67734451

Links

ENSG00000139988 ∙ NCBI:145226 ∙ OMIM:608830 ∙ HGNC:19977 ∙ Uniprot:Q96NR8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa (Supportive), mode of inheritance: AD
• Leber congenital amaurosis (Supportive), mode of inheritance: AD
• Leber congenital amaurosis 13 (Definitive), mode of inheritance: AR
• Leber congenital amaurosis 13 (Strong), mode of inheritance: AR
• Leber congenital amaurosis 13 (Strong), mode of inheritance: AD
• RDH12-related recessive retinopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leber congenital amaurosis 13; Retinitis pigmentosa 53	AD/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	15258582; 15322982; 16269441; 17197551; 18779497; 19140180; 19840725; 20736127; 22065924

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RDH12 gene.

• Leber congenital amaurosis 13 (435 variants)
• Leber congenital amaurosis (79 variants)
• not provided (53 variants)
• Retinitis pigmentosa (41 variants)
• Retinal dystrophy (33 variants)
• Retinitis Pigmentosa, Recessive (22 variants)
• Inborn genetic diseases (12 variants)
• Macular dystrophy (6 variants)
• not specified (5 variants)
• Cone-rod dystrophy (3 variants)
• Retinitis pigmentosa 53 (2 variants)
• Abnormality of the eye (2 variants)
• RDH12-related condition (1 variants)
• Rod-cone dystrophy (1 variants)
• RDH12-Related Disorders (1 variants)
• Stargardt disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RDH12 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			1	128	2	131
missense	13	33	120	2		168
nonsense	11	4				15
start loss			1			1
frameshift	19	12	1			32
inframe indel			3			3
splice donor/acceptor (+/-2bp)	7	11				18
splice region			11	25		36
non coding			15	34	19	68
Total	50	60	141	164	21

Highest pathogenic variant AF is 0.000105

Variants in RDH12

This is a list of pathogenic ClinVar variants found in the RDH12 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-67701947-C-T		Retinitis Pigmentosa, Recessive • Retinitis pigmentosa	Benign/Likely benign (Jan 13, 2018)
14-67720869-G-A		Retinitis Pigmentosa, Recessive • Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
14-67720874-C-G		Retinitis Pigmentosa, Recessive	Uncertain significance (Jun 14, 2016)
14-67722206-A-G			Benign (May 15, 2021)
14-67722491-A-G		Retinitis Pigmentosa, Recessive • Retinitis pigmentosa	Benign/Likely benign (Jan 13, 2018)
14-67722520-C-T		Retinitis Pigmentosa, Recessive	Uncertain significance (Apr 28, 2017)
14-67722522-G-A		Retinitis Pigmentosa, Recessive • Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
14-67722529-G-A		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
14-67722643-A-G		Leber congenital amaurosis 13	Uncertain significance (Sep 01, 2022)
14-67722644-T-C		Leber congenital amaurosis	Uncertain significance (Jul 24, 2023)
14-67722648-G-A		Leber congenital amaurosis 13	Likely benign (Dec 30, 2023)
14-67722648-G-C		Leber congenital amaurosis 13	Likely benign (Jun 08, 2022)
14-67722651-C-T		Leber congenital amaurosis 13	Likely benign (Dec 29, 2022)
14-67722656-T-TGGGACTGCTCACCTC		Leber congenital amaurosis 13	Uncertain significance (Apr 10, 2023)
14-67722660-A-G		Leber congenital amaurosis 13	Likely benign (Jul 19, 2022)
14-67722661-C-T		Leber congenital amaurosis 13	Likely benign (Dec 14, 2023)
14-67722663-G-A		Leber congenital amaurosis 13	Likely benign (Aug 17, 2023)
14-67722666-C-T		Leber congenital amaurosis 13	Likely benign (Feb 25, 2022)
14-67722667-ACCT-A		Leber congenital amaurosis 13 • Leber congenital amaurosis	Uncertain significance (Dec 08, 2021)
14-67722668-C-A		Leber congenital amaurosis 13	Uncertain significance (Jul 17, 2023)
14-67722668-C-T		Leber congenital amaurosis 13	Uncertain significance (Jul 20, 2022)
14-67722669-C-A		Leber congenital amaurosis 13	Likely benign (Nov 19, 2021)
14-67722671-CCTT-C		Leber congenital amaurosis 13	Uncertain significance (Aug 28, 2021)
14-67722672-C-T		Leber congenital amaurosis 13	Likely benign (Feb 10, 2022)
14-67722674-T-C		Leber congenital amaurosis 13	Uncertain significance (Mar 11, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RDH12	protein_coding	protein_coding	ENST00000551171	7	32567

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.26e-9	0.144	125656	0	92	125748	0.000366

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.142	182	177	1.03	0.0000110	2018
Missense in Polyphen		86	78.487	1.0957		924
Synonymous	-1.33	91	76.3	1.19	0.00000463	683
Loss of Function	0.292	14	15.2	0.919	0.00000113	156

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000866	0.000865
Ashkenazi Jewish	0.00	0.00
East Asian	0.000110	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000553	0.000545
Middle Eastern	0.000110	0.000109
South Asian	0.0000980	0.0000980
Other	0.000491	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Exhibits an oxidoreductive catalytic activity towards retinoids. Most efficient as an NADPH-dependent retinal reductase. Displays high activity toward 9-cis and all-trans-retinol. Also involved in the metabolism of short-chain aldehydes. No steroid dehydrogenase activity detected. Might be the key enzyme in the formation of 11-cis-retinal from 11-cis-retinol during regeneration of the cone visual pigments. {ECO:0000269|PubMed:12226107}.
• Disease: DISEASE: Retinitis pigmentosa 53 (RP53) [MIM:612712]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269|PubMed:19140180, ECO:0000269|PubMed:19956407}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Retinol metabolism - Homo sapiens (human);Vitamin A Deficiency;Retinol Metabolism;Vitamin A and Carotenoid Metabolism;Signaling by GPCR;Signal Transduction;The canonical retinoid cycle in rods (twilight vision);Visual signal transduction: Rods;retinol biosynthesis;G alpha (i) signalling events;Visual phototransduction;the visual cycle I (vertebrates);GPCR downstream signalling;Visual signal transduction: Cones (Consensus)

Recessive Scores

• pRec: 0.182

Intolerance Scores

• loftool: 0.289
• rvis_EVS: -0.65
• rvis_percentile_EVS: 16.44

Haploinsufficiency Scores

• pHI: 0.319
• hipred: N
• hipred_score: 0.248
• ghis: 0.596

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.896

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rdh12
• Phenotype: vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cellular phenotype

Gene ontology

• Biological process: retinoid metabolic process;visual perception;retinol metabolic process;photoreceptor cell maintenance;response to stimulus;oxidation-reduction process
• Cellular component: photoreceptor inner segment membrane
• Molecular function: retinol dehydrogenase activity;protein binding;NADP-retinol dehydrogenase activity