Retinitis pigmentosa 80

Summary

Retinitis pigmentosa 80 (MONDO:0054708) is a disease caused by IFT140 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: IFT140 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 535

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 80
Mondo ID	MONDO:0054708
OMIM	617781
DOID	DOID:0061111
UMLS	C4540439
MedGen	1619674
GARD	0016252
Is cancer (heuristic)	no

Also known as: RP80

Data availability: 535 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 80

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 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 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

535 retrieved; paginated sample, class counts are floors:

224 uncertain significance, 116 conflicting classifications of pathogenicity, 63 likely pathogenic, 52 likely benign, 33 pathogenic/likely pathogenic, 17 pathogenic, 16 benign/likely benign, 14 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1069388	NM_014714.4(IFT140):c.2500C>T (p.Arg834Ter)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071413	NM_014714.4(IFT140):c.1501C>T (p.Arg501Ter)	IFT140	Pathogenic	criteria provided, multiple submitters, no conflicts
1074487	NM_014714.4(IFT140):c.482dup (p.Pro162fs)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1184606	NM_014714.4(IFT140):c.1422_1423insAA (p.Arg475fs)	IFT140	Pathogenic	criteria provided, multiple submitters, no conflicts
1213850	NM_014714.4(IFT140):c.635-1G>C	IFT140	Pathogenic	criteria provided, single submitter
1298391	NM_014714.4(IFT140):c.2214_2217del (p.Asp738fs)	IFT140	Pathogenic	criteria provided, multiple submitters, no conflicts
1323104	NM_014714.4(IFT140):c.1359_1359+3delinsAC	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1325702	NM_014714.4(IFT140):c.1039C>T (p.Arg347Ter)	IFT140	Pathogenic	criteria provided, multiple submitters, no conflicts
1328335	NM_014714.4(IFT140):c.3214C>T (p.Arg1072Ter)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1373449	NM_014714.4(IFT140):c.2671del (p.Gln890_Val891insTer)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1398675	NM_014714.4(IFT140):c.2443C>T (p.Gln815Ter)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1417771	NM_014714.4(IFT140):c.919C>T (p.Arg307Ter)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1424674	NM_014714.4(IFT140):c.3408_3409del (p.His1136fs)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1428555	NM_014714.4(IFT140):c.2038C>T (p.Gln680Ter)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1451353	NM_014714.4(IFT140):c.490G>T (p.Glu164Ter)	IFT140	Pathogenic	criteria provided, multiple submitters, no conflicts
1459143	NM_014714.4(IFT140):c.1513C>T (p.Arg505Ter)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1905580	NM_014714.4(IFT140):c.2483del (p.Gly828fs)	IFT140	Pathogenic	criteria provided, multiple submitters, no conflicts
1973713	NM_014714.4(IFT140):c.2682delinsAA (p.His894fs)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1980756	NM_014714.4(IFT140):c.4041-2A>G	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2017130	NM_014714.4(IFT140):c.565del (p.Ser189fs)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2104731	NM_014714.4(IFT140):c.1597_1598insA (p.Phe533fs)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2444130	NM_014714.4(IFT140):c.1246C>T (p.Gln416Ter)	IFT140	Pathogenic	criteria provided, multiple submitters, no conflicts
2630877	NM_014714.4(IFT140):c.308_309del (p.Thr103fs)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
280884	NM_014714.4(IFT140):c.1010-1G>A	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2910387	NM_014714.4(IFT140):c.3060C>G (p.Tyr1020Ter)	IFT140	Pathogenic	criteria provided, multiple submitters, no conflicts
31679	NM_014714.4(IFT140):c.1990G>A (p.Glu664Lys)	IFT140	Pathogenic	criteria provided, multiple submitters, no conflicts
31680	NM_014714.4(IFT140):c.2399+1G>T	IFT140	Pathogenic	criteria provided, multiple submitters, no conflicts
31683	NM_014714.4(IFT140):c.634G>A (p.Gly212Arg)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
31684	NM_014714.4(IFT140):c.3916dup (p.Ala1306fs)	IFT140	Pathogenic	criteria provided, multiple submitters, no conflicts
3234075	NM_014714.4(IFT140):c.168_171del (p.His57fs)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 5 · 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
IFT140	Strong	Autosomal recessive	retinitis pigmentosa 80	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IFT140	Orphanet:140969	Saldino-Mainzer syndrome
IFT140	Orphanet:474	Jeune syndrome
IFT140	Orphanet:65	Leber congenital amaurosis
IFT140	Orphanet:730	Autosomal dominant polycystic kidney disease
IFT140	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
IFT140	HGNC:29077	ENSG00000187535	Q96RY7	Intraflagellar transport protein 140 homolog	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IFT140	Intraflagellar transport protein 140 homolog	Component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs).

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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IFT140	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_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
left lobe of thyroid gland	1
right lobe of thyroid gland	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IFT140	214	ubiquitous	marker	right uterine tube, right lobe of thyroid gland, left lobe of thyroid gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IFT140	1,602

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IFT140	Q96RY7	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Intraflagellar transport	1	200.3×	0.006	IFT140
Hedgehog ‘off’ state	1	178.4×	0.006	IFT140

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
neural tube patterning	1	2808.7×	0.003	IFT140
embryonic camera-type eye development	1	1203.7×	0.003	IFT140
intraciliary retrograde transport	1	1123.5×	0.003	IFT140
photoreceptor cell outer segment organization	1	1053.2×	0.003	IFT140
embryonic brain development	1	802.5×	0.003	IFT140
regulation of smoothened signaling pathway	1	624.1×	0.003	IFT140
regulation of cilium assembly	1	601.9×	0.003	IFT140
embryonic cranial skeleton morphogenesis	1	581.1×	0.003	IFT140
protein localization to cilium	1	401.2×	0.004	IFT140
embryonic digit morphogenesis	1	300.9×	0.004	IFT140
non-motile cilium assembly	1	290.6×	0.004	IFT140
determination of left/right symmetry	1	255.3×	0.005	IFT140
heart development	1	78.8×	0.014	IFT140
cilium assembly	1	73.6×	0.014	IFT140

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
IFT140	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	IFT140

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)
IFT140	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.