Retinitis pigmentosa 17

Summary

Retinitis pigmentosa 17 (MONDO:0010945) is a disease caused by CA4 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CA4 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 17
Mondo ID	MONDO:0010945
MeSH	C563437
OMIM	600852
DOID	DOID:0110404
UMLS	C1833245
MedGen	322153
GARD	0010387
Is cancer (heuristic)	no

Also known as: CA4 retinitis pigmentosa · retinitis pigmentosa 17 · retinitis pigmentosa caused by mutation in CA4 · retinitis pigmentosa type 17 · RP 17 · RP17

Data availability: 6 ClinVar variants · 1 GenCC gene-disease record.

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 17

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 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 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

6 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 3 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
17607	NM_000717.5(CA4):c.40C>T (p.Arg14Trp)	CA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
17609	NM_000717.5(CA4):c.206G>A (p.Arg69His)	CA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
445984	NM_000717.5(CA4):c.*59G>A	CA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1011596	NM_000717.5(CA4):c.680C>T (p.Pro227Leu)	CA4	Uncertain significance	criteria provided, multiple submitters, no conflicts
17608	NM_000717.5(CA4):c.655C>A (p.Arg219Ser)	CA4	Uncertain significance	no assertion criteria provided
3671603	NM_000717.5(CA4):c.260G>A (p.Gly87Glu)	CA4	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
CA4	Strong	Autosomal dominant	retinitis pigmentosa 17	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CA4	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
CA4	HGNC:1375	ENSG00000167434	P22748	Carbonic anhydrase 4	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CA4	Carbonic anhydrase 4	Catalyzes the reversible hydration of carbon dioxide into bicarbonate and protons and thus is essential to maintaining intracellular and extracellular pH.

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CA4	Enzyme (other)	yes	4.2.1.1	CA_dom, Carbonic_anhydrase_a-class_CS, Carbonic_anhydrase_a-class

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
cerebellar hemisphere	1
mucosa of transverse colon	1
rectum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CA4	245	broad	marker	mucosa of transverse colon, rectum, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CA4	2,196

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CA4	P22748	10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Erythrocytes take up oxygen and release carbon dioxide	1	1268.9×	0.002	CA4
O2/CO2 exchange in erythrocytes	1	1268.9×	0.002	CA4
Reversible hydration of carbon dioxide	1	951.7×	0.002	CA4
Erythrocytes take up carbon dioxide and release oxygen	1	878.5×	0.002	CA4
Transport of small molecules	1	25.1×	0.048	CA4
Metabolism	1	11.6×	0.086	CA4

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
bicarbonate transport	1	802.5×	0.001	CA4

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
CA4	METHAZOLAMIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CA4	59	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
METHAZOLAMIDE	4	CA4
ACETAZOLAMIDE	4	CA4
ZONISAMIDE	4	CA4
TRICHLORMETHIAZIDE	4	CA4
CHLORTHALIDONE	4	CA4
SODIUM PHOSPHATE, DIBASIC, ANHYDROUS	4	CA4
ACETAMINOPHEN	4	CA4
POTASSIUM IODIDE	4	CA4
CELECOXIB	4	CA4
PYRITHIONE ZINC	4	CA4
POTASSIUM CHLORIDE	4	CA4
LEVETIRACETAM	4	CA4
SODIUM CITRATE	4	CA4
SODIUM BENZOATE	4	CA4
PHENOL	4	CA4
DICHLORPHENAMIDE	4	CA4
ETHOXZOLAMIDE	4	CA4
SULFANILAMIDE	4	CA4
VERALIPRIDE	4	CA4
DORZOLAMIDE	4	CA4
BRINZOLAMIDE	4	CA4
TOPIRAMATE	4	CA4
NILOTINIB	4	CA4
BORTEZOMIB	4	CA4
FUROSEMIDE	4	CA4
INDAPAMIDE	4	CA4
MAFENIDE	4	CA4
SALICYLIC ACID	4	CA4
HYDROQUINONE	4	CA4
LACOSAMIDE	4	CA4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CA4	202	Binding:195, ADMET:6, Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CA4	4.2.1.1	carbonic anhydrase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CA4	202

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)
METHAZOLAMIDE	4	CA4
ACETAZOLAMIDE	4	CA4
ZONISAMIDE	4	CA4
TRICHLORMETHIAZIDE	4	CA4
CHLORTHALIDONE	4	CA4
SODIUM PHOSPHATE, DIBASIC, ANHYDROUS	4	CA4
ACETAMINOPHEN	4	CA4
POTASSIUM IODIDE	4	CA4
CELECOXIB	4	CA4
PYRITHIONE ZINC	4	CA4
POTASSIUM CHLORIDE	4	CA4
LEVETIRACETAM	4	CA4
SODIUM CITRATE	4	CA4
SODIUM BENZOATE	4	CA4
PHENOL	4	CA4
DICHLORPHENAMIDE	4	CA4
ETHOXZOLAMIDE	4	CA4
SULFANILAMIDE	4	CA4
VERALIPRIDE	4	CA4
DORZOLAMIDE	4	CA4
BRINZOLAMIDE	4	CA4
TOPIRAMATE	4	CA4
NILOTINIB	4	CA4
BORTEZOMIB	4	CA4
FUROSEMIDE	4	CA4
INDAPAMIDE	4	CA4
MAFENIDE	4	CA4
SALICYLIC ACID	4	CA4
HYDROQUINONE	4	CA4
LACOSAMIDE	4	CA4

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CA4
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.