Retinitis pigmentosa 78

disease

On this page

Also known as RP78

Summary

Retinitis pigmentosa 78 (MONDO:0044314) is a disease caused by ARHGEF18 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: ARHGEF18 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 22

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 78
Mondo ID	MONDO:0044314
OMIM	617433
DOID	DOID:0061113
UMLS	C4479481
MedGen	1378790
GARD	0016229
Is cancer (heuristic)	no

Also known as: retinitis pigmentosa 78 · RP78

Data availability: 22 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 78

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

22 retrieved; paginated sample, class counts are floors:

12 uncertain significance, 5 likely pathogenic, 3 pathogenic, 1 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
417755	NM_001367823.1(ARHGEF18):c.2560C>T (p.Arg854Ter)	ARHGEF18	Pathogenic	criteria provided, single submitter
417756	NM_001367823.1(ARHGEF18):c.3302_3325del (p.Arg1101_Glu1108del)	ARHGEF18	Pathogenic	no assertion criteria provided
417757	NM_001367823.1(ARHGEF18):c.3196G>T (p.Glu1066Ter)	ARHGEF18	Pathogenic	criteria provided, single submitter
417758	NM_001367823.1(ARHGEF18):c.2181+5G>A	ARHGEF18	Pathogenic/Likely pathogenic	no assertion criteria provided
1031128	NM_001367823.1(ARHGEF18):c.2905-1G>T	ARHGEF18	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3393420	NM_001367823.1(ARHGEF18):c.275+1G>T	ARHGEF18	Likely pathogenic	criteria provided, single submitter
3892982	NM_001367823.1(ARHGEF18):c.294dup (p.Ala99fs)	ARHGEF18	Likely pathogenic	criteria provided, single submitter
417754	NM_001367823.1(ARHGEF18):c.1372A>G (p.Thr458Ala)	ARHGEF18	Likely pathogenic	criteria provided, single submitter
4849288	NM_001367823.1(ARHGEF18):c.112del (p.Ala40fs)	ARHGEF18	Likely pathogenic	criteria provided, single submitter
1957000	NM_001367823.1(ARHGEF18):c.968-251G>A	ARHGEF18	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1023463	NM_001367823.1(ARHGEF18):c.2717C>T (p.Pro906Leu)	ARHGEF18	Uncertain significance	criteria provided, single submitter
1033723	NM_001367823.1(ARHGEF18):c.2089T>G (p.Ser697Ala)	ARHGEF18	Uncertain significance	criteria provided, single submitter
1034733	NM_001367823.1(ARHGEF18):c.1769T>G (p.Leu590Arg)	ARHGEF18	Uncertain significance	criteria provided, multiple submitters, no conflicts
1433026	NM_001367823.1(ARHGEF18):c.1904A>G (p.Lys635Arg)	ARHGEF18	Uncertain significance	criteria provided, multiple submitters, no conflicts
1434263	NM_001367823.1(ARHGEF18):c.1105G>C (p.Gly369Arg)	ARHGEF18	Uncertain significance	criteria provided, multiple submitters, no conflicts
1473157	NM_001367823.1(ARHGEF18):c.1537C>T (p.Arg513Cys)	ARHGEF18	Uncertain significance	criteria provided, multiple submitters, no conflicts
1803233	NM_001367823.1(ARHGEF18):c.3161C>T (p.Ala1054Val)	ARHGEF18	Uncertain significance	criteria provided, single submitter
4078010	NM_001367823.1(ARHGEF18):c.2070G>T (p.Met690Ile)	ARHGEF18	Uncertain significance	criteria provided, single submitter
814002	NM_001367823.1(ARHGEF18):c.1469G>T (p.Arg490Leu)	ARHGEF18	Uncertain significance	criteria provided, multiple submitters, no conflicts
814003	NM_001367823.1(ARHGEF18):c.3580C>T (p.Arg1194Cys)	ARHGEF18	Uncertain significance	criteria provided, multiple submitters, no conflicts
939165	NM_001367823.1(ARHGEF18):c.968-75G>A	ARHGEF18	Uncertain significance	criteria provided, multiple submitters, no conflicts
964524	NM_001367823.1(ARHGEF18):c.1006G>T (p.Asp336Tyr)	ARHGEF18	Uncertain significance	criteria provided, single submitter

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
ARHGEF18	Strong	Autosomal recessive	retinitis pigmentosa 78	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ARHGEF18	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
ARHGEF18	HGNC:17090	ENSG00000104880	Q6ZSZ5	Rho guanine nucleotide exchange factor 18	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ARHGEF18	Rho guanine nucleotide exchange factor 18	Acts as a guanine nucleotide exchange factor (GEF) for RhoA GTPases.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ARHGEF18	Transcription factor	no		DH_dom, PH_domain, PH-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
ileal mucosa	1
pancreatic ductal cell	1
thymus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ARHGEF18	284	ubiquitous	marker	pancreatic ductal cell, thymus, ileal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ARHGEF18	880

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ARHGEF18	Q6ZSZ5	62.10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. 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
TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)	1	671.8×	0.017	ARHGEF18
Cell death signalling via NRAGE, NRIF and NADE	1	219.6×	0.017	ARHGEF18
Signaling by TGF-beta Receptor Complex	1	200.3×	0.017	ARHGEF18
p75 NTR receptor-mediated signalling	1	187.2×	0.017	ARHGEF18
NRAGE signals death through JNK	1	184.2×	0.017	ARHGEF18
Death Receptor Signaling	1	139.3×	0.017	ARHGEF18
G alpha (12/13) signalling events	1	137.6×	0.017	ARHGEF18
Signaling by TGFB family members	1	115.3×	0.017	ARHGEF18
RHOA GTPase cycle	1	74.6×	0.024	ARHGEF18
RAC1 GTPase cycle	1	61.1×	0.024	ARHGEF18
RHO GTPase cycle	1	60.1×	0.024	ARHGEF18
GPCR downstream signalling	1	43.4×	0.031	ARHGEF18
Signaling by GPCR	1	40.1×	0.031	ARHGEF18
Signaling by Rho GTPases	1	34.2×	0.032	ARHGEF18
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.032	ARHGEF18
Signal Transduction	1	10.2×	0.098	ARHGEF18

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
protein localization to cell-cell junction	1	1872.4×	0.003	ARHGEF18
negative regulation of stress fiber assembly	1	581.1×	0.004	ARHGEF18
regulation of Rho protein signal transduction	1	510.7×	0.004	ARHGEF18
small GTPase-mediated signal transduction	1	183.2×	0.008	ARHGEF18
regulation of cell shape	1	123.0×	0.010	ARHGEF18
actin cytoskeleton organization	1	79.1×	0.013	ARHGEF18

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ARHGEF18	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

0 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.

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	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	ARHGEF18

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ARHGEF18	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: ARHGEF18