Retinitis pigmentosa 62

Summary

Retinitis pigmentosa 62 (MONDO:0013611) is a disease caused by MAK (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: MAK (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 40

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 62
Mondo ID	MONDO:0013611
OMIM	614181
DOID	DOID:0110380
UMLS	C3280042
MedGen	481672
GARD	0015767
Is cancer (heuristic)	no

Also known as: MAK retinitis pigmentosa · retinitis pigmentosa 62 · retinitis pigmentosa caused by mutation in MAK · retinitis pigmentosa type 62 · RP62

Data availability: 40 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › inherited retinal dystrophy › retinitis pigmentosa › retinitis pigmentosa 62

Related subtypes (101): retinitis pigmentosa 6, cone-rod dystrophy 2, retinitis pigmentosa 1, retinitis pigmentosa 9, retinitis pigmentosa 10, dominant pericentral pigmentary retinopathy, late-adult onset retinitis pigmentosa, autosomal recessive pericentral pigmentary retinopathy, retinitis pigmentosa 3, retinitis pigmentosa 24, retinitis pigmentosa 23, retinitis pigmentosa 34, retinitis pigmentosa 2, retinitis pigmentosa Y-linked, retinitis pigmentosa 13, retinitis pigmentosa 12, retinitis pigmentosa 14, retinitis pigmentosa 11, retinitis pigmentosa 17, retinitis pigmentosa 18, retinitis pigmentosa 19, retinitis pigmentosa 22, retinitis pigmentosa 25, retinitis pigmentosa 28, retinitis pigmentosa 30, retinitis pigmentosa 7, retinitis pigmentosa 26, retinitis pigmentosa 32, retinitis pigmentosa 31, retinitis pigmentosa 35, retinitis pigmentosa 33, retinitis pigmentosa 36, retinitis pigmentosa 37, retinitis pigmentosa 41, retinitis pigmentosa 29, retinitis pigmentosa 46, retinitis pigmentosa 42, retinitis pigmentosa 50, retinitis pigmentosa 54, retinitis pigmentosa 51, retinitis pigmentosa 55, retinitis pigmentosa 56, retinitis pigmentosa 57, retinitis pigmentosa 58, cone-rod dystrophy 15, retinitis pigmentosa 4, retinitis pigmentosa 27, retinitis pigmentosa 49, retinitis pigmentosa 47, retinitis pigmentosa 45, retinitis pigmentosa 44, retinitis pigmentosa 20, retinitis pigmentosa 40, retinitis pigmentosa 39, retinitis pigmentosa 43, retinitis pigmentosa 48, retinitis pigmentosa 59, retinitis pigmentosa 38, retinitis pigmentosa 60, retinitis pigmentosa 61, retinitis pigmentosa 63, cone-rod dystrophy 16, retinitis pigmentosa 66, retinitis pigmentosa with or without situs inversus, retinitis pigmentosa 67, retinitis pigmentosa 68, retinitis pigmentosa 69, retinitis pigmentosa 70, retinal dystrophy and obesity, retinitis pigmentosa 71, retinitis pigmentosa 72, retinitis pigmentosa 73, retinitis pigmentosa 74, retinitis pigmentosa 75, retinitis pigmentosa 76, retinitis pigmentosa 77, retinitis pigmentosa 92, retinitis pigmentosa 93, retinitis pigmentosa 83, retinitis pigmentosa 84, retinitis pigmentosa 85, retinitis pigmentosa 86, retinitis pigmentosa 87 with choroidal involvement, retinitis pigmentosa 88, retinitis pigmentosa 90, retinitis pigmentosa 81, retinitis pigmentosa 78, retinitis pigmentosa 79, retinitis pigmentosa 80, retinitis pigmentosa 94, variable age at onset, retinitis pigmentosa 53, retinitis pigmentosa 65, retinitis pigmentosa 64, retinitis pigmentosa 95, retinitis pigmentosa 96, retinitis pigmentosa 97, retinitis pigmentosa 98, retinitis pigmentosa 99, retinitis pigmentosa 100, retinitis pigmentosa 101, retinitis pigmentosa 7, digenic

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

40 retrieved; paginated sample, class counts are floors:

13 pathogenic/likely pathogenic, 7 uncertain significance, 7 pathogenic, 6 likely pathogenic, 4 conflicting classifications of pathogenicity, 2 benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1039131	NM_001242957.3(MAK):c.79G>A (p.Gly27Arg)	MAK	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070586	NM_001242957.3(MAK):c.1222del (p.Glu408fs)	MAK	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072281	NM_001242957.3(MAK):c.7C>T (p.Arg3Ter)	MAK	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
143121	NM_001242957.3(MAK):c.340dup (p.Ala114fs)	MAK	Pathogenic	criteria provided, multiple submitters, no conflicts
1810762	NM_001242957.3(MAK):c.7_10dup (p.Tyr4fs)	MAK	Pathogenic	criteria provided, single submitter
1976258	NM_001242957.3(MAK):c.394_395insCTTC (p.Leu132fs)	MAK	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2579195	NM_001242957.3:c.1297_1298insAlu	MAK	Pathogenic	criteria provided, single submitter
2809478	NM_001242957.3(MAK):c.1741C>T (p.Gln581Ter)	MAK	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
286531	NM_001242957.3(MAK):c.170_171del (p.Leu57fs)	MAK	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2893031	NM_001242957.3(MAK):c.947dup (p.Leu316fs)	MAK	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2957025	NM_001242957.3(MAK):c.1294dup (p.Arg432fs)	MAK	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
29780	MAK, 353-BP ALU INS, EX9	MAK	Pathogenic	no assertion criteria provided
29781	NM_001242957.3(MAK):c.718C>T (p.Gln240Ter)	MAK	Pathogenic	no assertion criteria provided
29784	NM_001242957.3(MAK):c.497G>A (p.Arg166His)	MAK	Pathogenic	criteria provided, multiple submitters, no conflicts
632469	NM_001242957.3(MAK):c.1698C>A (p.Tyr566Ter)	MAK	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
636040	NM_001242957.3(MAK):c.814C>T (p.Arg272Ter)	MAK	Pathogenic	criteria provided, multiple submitters, no conflicts
849391	NM_001242957.3(MAK):c.79G>C (p.Gly27Arg)	MAK	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
866153	NM_001242957.3(MAK):c.1356_1357del (p.Glu454fs)	MAK	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
951172	NM_001242957.3(MAK):c.1087_1088del (p.Gln364fs)	MAK	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
958267	NM_001242957.3(MAK):c.1600G>T (p.Glu534Ter)	MAK	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065773	NM_001242957.3(MAK):c.1143+2_1143+3del	MAK	Likely pathogenic	criteria provided, single submitter
1065774	NM_001242957.3(MAK):c.366dup (p.His123fs)	MAK	Likely pathogenic	criteria provided, single submitter
1518471	NM_001242957.3(MAK):c.832-1G>C	MAK	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2920630	NM_001242957.3(MAK):c.104T>A (p.Met35Lys)	MAK	Likely pathogenic	no assertion criteria provided
29782	NM_001242957.3(MAK):c.388A>C (p.Asn130His)	MAK	Likely pathogenic	criteria provided, single submitter
3362527	NM_001242957.3(MAK):c.168del (p.Lys56fs)	MAK	Likely pathogenic	criteria provided, single submitter
1435408	NM_001242957.3(MAK):c.1143+6T>C	MAK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
29783	NM_001242957.3(MAK):c.37G>A (p.Gly13Ser)	MAK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
783454	NM_001242957.3(MAK):c.1477AAG[1] (p.Lys494del)	MAK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
951611	NM_001242957.3(MAK):c.1834G>C (p.Gly612Arg)	MAK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
MAK	Definitive	Autosomal recessive	retinitis pigmentosa 62	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MAK	Orphanet:791	Retinitis pigmentosa

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MAK	HGNC:6816	ENSG00000111837	P20794	Serine/threonine-protein kinase MAK	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MAK	Serine/threonine-protein kinase MAK	Essential for the regulation of ciliary length and required for the long-term survival of photoreceptors.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MAK	Kinase	yes	2.7.11.22	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
choroid plexus epithelium	1
male germ cell	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MAK	184	broad	marker	sperm, male germ cell, choroid plexus epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MAK	966

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MAK	P20794	62.74

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of non-motile cilium assembly	1	8426.0×	0.001	MAK
intraciliary transport	1	561.7×	0.009	MAK
photoreceptor cell maintenance	1	358.6×	0.009	MAK
non-motile cilium assembly	1	290.6×	0.009	MAK
protein autophosphorylation	1	145.3×	0.014	MAK
cilium assembly	1	73.6×	0.021	MAK
protein phosphorylation	1	68.0×	0.021	MAK
intracellular signal transduction	1	38.1×	0.032	MAK
spermatogenesis	1	35.2×	0.032	MAK
cell differentiation	1	29.1×	0.034	MAK

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MAK	7	3

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ALVOCIDIB	3	MAK
LESTAURTINIB	3	MAK
FORETINIB	2	MAK
RG-547	2	MAK
AT-7519	2	MAK
BMS-387032	1	MAK
AST-487	1	MAK

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
MAK	94	Binding:94

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MAK	2.7.11.22	cyclin-dependent kinase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

7 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
ALVOCIDIB	3	MAK
LESTAURTINIB	3	MAK
FORETINIB	2	MAK
RG-547	2	MAK
AT-7519	2	MAK
BMS-387032	1	MAK
AST-487	1	MAK

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	1	MAK
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.