Retinitis pigmentosa 38

Summary

Retinitis pigmentosa 38 (MONDO:0013469) is a disease caused by MERTK (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: MERTK (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 101

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 38
Mondo ID	MONDO:0013469
OMIM	613862
DOID	DOID:0110367
UMLS	C3151228
MedGen	462578
GARD	0015725
Is cancer (heuristic)	no

Also known as: MERTK retinitis pigmentosa · retinitis pigmentosa 38 · retinitis pigmentosa caused by mutation in MERTK · retinitis pigmentosa type 38 · RP38

Data availability: 101 ClinVar variants · 3 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 38

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 60, retinitis pigmentosa 61, retinitis pigmentosa 62, 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

101 retrieved; paginated sample, class counts are floors:

32 pathogenic, 18 uncertain significance, 14 benign, 13 likely pathogenic, 11 conflicting classifications of pathogenicity, 7 pathogenic/likely pathogenic, 4 benign/likely benign, 1 likely benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1065647	NM_006343.3(MERTK):c.1090G>T (p.Glu364Ter)	LOC112806037	Pathogenic	criteria provided, multiple submitters, no conflicts
2579232	GRCh38/hg38 2q13(chr2:111940205-112055854)x1	LOC112806037	Pathogenic	criteria provided, single submitter
2579252	GRCh38/hg38 2q13(chr2:111940205-112029659)x0	LOC112806037	Pathogenic	criteria provided, single submitter
3341289	Single allele	LOC112806037	Pathogenic	criteria provided, single submitter
801735	NM_006343.3(MERTK):c.992_993del (p.Ser331fs)	LOC112806037	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065760	NM_006343.3(MERTK):c.2190-1G>T	MERTK	Pathogenic	criteria provided, single submitter
1067939	NM_006343.3(MERTK):c.1868-1G>A	MERTK	Pathogenic	criteria provided, multiple submitters, no conflicts
1330299	NM_006343.3(MERTK):c.2190-2A>G	MERTK	Pathogenic	criteria provided, single submitter
143139	NM_006343.3(MERTK):c.225del (p.Gly76fs)	MERTK	Pathogenic	criteria provided, multiple submitters, no conflicts
1691718	NM_006343.3(MERTK):c.1647T>G (p.Tyr549Ter)	MERTK	Pathogenic	criteria provided, single submitter
191123	NM_006343.3(MERTK):c.325A>T (p.Lys109Ter)	MERTK	Pathogenic	criteria provided, single submitter
191124	NM_006343.3(MERTK):c.1604+2T>G	MERTK	Pathogenic	criteria provided, single submitter
2110010	NM_006343.3(MERTK):c.912G>A (p.Trp304Ter)	MERTK	Pathogenic	criteria provided, multiple submitters, no conflicts
2203132	NM_006343.3(MERTK):c.296_297del (p.Thr99fs)	MERTK	Pathogenic	criteria provided, multiple submitters, no conflicts
2203136	NM_006343.3(MERTK):c.2377del (p.Glu792_Ile793insTer)	MERTK	Pathogenic	criteria provided, multiple submitters, no conflicts
224739	NM_006343.2:c.-8163_c.1145-1213del	MERTK	Pathogenic	no assertion criteria provided
2579237	GRCh38/hg38 2q13(chr2:111993999-111994721)x1	MERTK	Pathogenic	criteria provided, single submitter
265244	NM_006343.3(MERTK):c.2214del (p.Cys738fs)	MERTK	Pathogenic	criteria provided, multiple submitters, no conflicts
2734259	NM_006343.3(MERTK):c.721C>T (p.Gln241Ter)	MERTK	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
37302	NG_011607.1:g.(86577_89228)_(89381_96385)del	MERTK	Pathogenic	no assertion criteria provided
37303	NM_006343.3(MERTK):c.61+1G>A	MERTK	Pathogenic	no assertion criteria provided
37304	NC_000002.10:g.112364620_112455677del	MERTK	Pathogenic	no assertion criteria provided
37305	NM_006343.3(MERTK):c.2323C>T (p.Arg775Ter)	MERTK	Pathogenic	criteria provided, multiple submitters, no conflicts
437469	NM_006343.3(MERTK):c.584-1G>T	MERTK	Pathogenic	criteria provided, single submitter
437995	NM_006343.3(MERTK):c.2164C>T (p.Arg722Ter)	MERTK	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
522500	NM_006343.3(MERTK):c.2486+1G>A	MERTK	Pathogenic	no assertion criteria provided
5401	NM_006343.3(MERTK):c.1605-2A>G	MERTK	Pathogenic	criteria provided, multiple submitters, no conflicts
5402	NM_006343.3(MERTK):c.1951C>T (p.Arg651Ter)	MERTK	Pathogenic	criteria provided, multiple submitters, no conflicts
5403	NM_006343.3(MERTK):c.2189+1G>T	MERTK	Pathogenic	criteria provided, multiple submitters, no conflicts
636044	NM_006343.3(MERTK):c.345C>G (p.Cys115Trp)	MERTK	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
MERTK	Definitive	Autosomal recessive	retinitis pigmentosa 38	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MERTK	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
MERTK	HGNC:7027	ENSG00000153208	Q12866	Tyrosine-protein kinase Mer	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MERTK	Tyrosine-protein kinase Mer	Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6.

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)
MERTK	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub

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
mucosa of stomach	1
right adrenal gland	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MERTK	246	ubiquitous	marker	right adrenal gland cortex, mucosa of stomach, right adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MERTK	2,735

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MERTK	Q12866	42

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways 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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Dengue Virus Attachment and Entry	1	259.6×	0.012	MERTK
Cell surface interactions at the vascular wall	1	95.2×	0.016	MERTK
Hemostasis	1	36.0×	0.028	MERTK

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 leukocyte apoptotic process	1	8426.0×	0.002	MERTK
negative regulation of lymphocyte activation	1	5617.3×	0.002	MERTK
neutrophil clearance	1	2808.7×	0.002	MERTK
secretion by cell	1	1685.2×	0.003	MERTK
vagina development	1	1532.0×	0.003	MERTK
natural killer cell differentiation	1	887.0×	0.004	MERTK
negative regulation of cytokine production	1	510.7×	0.006	MERTK
substrate adhesion-dependent cell spreading	1	343.9×	0.007	MERTK
positive regulation of phagocytosis	1	318.0×	0.007	MERTK
platelet activation	1	267.5×	0.007	MERTK
retina development in camera-type eye	1	255.3×	0.007	MERTK
phagocytosis	1	240.7×	0.007	MERTK
cell surface receptor protein tyrosine kinase signaling pathway	1	173.7×	0.009	MERTK
establishment of localization in cell	1	160.5×	0.009	MERTK
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	78.4×	0.018	MERTK
cell-cell signaling	1	69.6×	0.018	MERTK
protein phosphorylation	1	68.0×	0.018	MERTK
cell surface receptor signaling pathway	1	64.1×	0.018	MERTK
cell migration	1	61.5×	0.018	MERTK
nervous system development	1	45.9×	0.023	MERTK
spermatogenesis	1	35.2×	0.028	MERTK

Therapeutics

Drug target analysis

Approved (phase 4): 1 · 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).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
MERTK	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MERTK	48	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	MERTK
AXITINIB	4	MERTK
SORAFENIB	4	MERTK
NERATINIB	4	MERTK
CABOZANTINIB	4	MERTK
VANDETANIB	4	MERTK
BOSUTINIB	4	MERTK
FILGOTINIB	4	MERTK
PACLITAXEL	4	MERTK
PAZOPANIB	4	MERTK
NINTEDANIB	4	MERTK
SUNITINIB	4	MERTK
ERLOTINIB	4	MERTK
QUIZARTINIB	4	MERTK
CRIZOTINIB	4	MERTK
MIDOSTAURIN	4	MERTK
LINIFANIB	3	MERTK
ITACITINIB	3	MERTK
ALVOCIDIB	3	MERTK
SURUFATINIB	3	MERTK
CEDIRANIB	3	MERTK
POVORCITINIB	3	MERTK
DOVITINIB	3	MERTK
LESTAURTINIB	3	MERTK
DORAMAPIMOD	2	MERTK
FORETINIB	2	MERTK
TANDUTINIB	2	MERTK
SU-014813	2	MERTK
REBASTINIB	2	MERTK
MK-2461	2	MERTK

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
MERTK	443	Binding:442, Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MERTK	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
MERTK	443

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

30 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)
FEDRATINIB	4	MERTK
AXITINIB	4	MERTK
SORAFENIB	4	MERTK
NERATINIB	4	MERTK
CABOZANTINIB	4	MERTK
VANDETANIB	4	MERTK
BOSUTINIB	4	MERTK
FILGOTINIB	4	MERTK
PACLITAXEL	4	MERTK
PAZOPANIB	4	MERTK
NINTEDANIB	4	MERTK
SUNITINIB	4	MERTK
ERLOTINIB	4	MERTK
QUIZARTINIB	4	MERTK
CRIZOTINIB	4	MERTK
MIDOSTAURIN	4	MERTK
LINIFANIB	3	MERTK
ITACITINIB	3	MERTK
ALVOCIDIB	3	MERTK
SURUFATINIB	3	MERTK
CEDIRANIB	3	MERTK
POVORCITINIB	3	MERTK
DOVITINIB	3	MERTK
LESTAURTINIB	3	MERTK
DORAMAPIMOD	2	MERTK
FORETINIB	2	MERTK
TANDUTINIB	2	MERTK
SU-014813	2	MERTK
REBASTINIB	2	MERTK
MK-2461	2	MERTK

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	MERTK
B	Phased (≥1) drug, not yet approved	0
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.