Retinitis pigmentosa 76

Summary

Retinitis pigmentosa 76 (MONDO:0014929) is a disease caused by POMGNT1 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: POMGNT1 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 92

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 76
Mondo ID	MONDO:0014929
OMIM	617123
DOID	DOID:0061103
UMLS	C4310704
MedGen	934671
GARD	0016196
Is cancer (heuristic)	no

Also known as: POMGNT1 retinitis pigmentosa · retinitis pigmentosa 76 · retinitis pigmentosa 76; RP76 · retinitis pigmentosa caused by mutation in POMGNT1 · retinitis pigmentosa type 76 · RP76

Data availability: 92 ClinVar variants · 2 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 76

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 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

92 retrieved; paginated sample, class counts are floors:

22 uncertain significance, 20 pathogenic/likely pathogenic, 16 conflicting classifications of pathogenicity, 15 likely pathogenic, 9 benign, 9 pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1499469	NM_017739.4(POMGNT1):c.1785+1G>A	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
254274	NM_017739.4(POMGNT1):c.1505G>C (p.Gly502Ala)	POMGNT1	Pathogenic	no assertion criteria provided
254275	NM_017739.4(POMGNT1):c.359T>G (p.Leu120Arg)	POMGNT1	Pathogenic	no assertion criteria provided
265399	NM_017739.4(POMGNT1):c.636C>T (p.Phe212=)	POMGNT1	Pathogenic	criteria provided, multiple submitters, no conflicts
370969	NM_017739.4(POMGNT1):c.1694_1695del (p.Ser565fs)	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3993	NM_017739.4(POMGNT1):c.932G>A (p.Arg311Gln)	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3994	NM_017739.4(POMGNT1):c.187C>T (p.Arg63Ter)	POMGNT1	Pathogenic	criteria provided, multiple submitters, no conflicts
4000	NM_017739.4(POMGNT1):c.1469G>A (p.Cys490Tyr)	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
558512	NM_017739.4(POMGNT1):c.385C>T (p.Arg129Trp)	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
56578	NM_017739.4(POMGNT1):c.1285-2A>G	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
56582	NM_017739.4(POMGNT1):c.1539+1G>A	POMGNT1	Pathogenic	criteria provided, multiple submitters, no conflicts
56591	NM_017739.4(POMGNT1):c.1876del (p.Val626fs)	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
56593	NM_017739.4(POMGNT1):c.1895+1G>T	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
56610	NM_017739.4(POMGNT1):c.931C>T (p.Arg311Ter)	POMGNT1	Pathogenic	criteria provided, multiple submitters, no conflicts
872288	NM_017739.4(POMGNT1):c.1325G>A (p.Arg442His)	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1412185	NM_017739.4(POMGNT1):c.1686dup (p.Glu563Ter)	TSPAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1455081	NM_017739.4(POMGNT1):c.1080del (p.Ile361fs)	TSPAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1525403	NM_017739.4(POMGNT1):c.880-1G>C	TSPAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2158255	NM_017739.4(POMGNT1):c.1609A>T (p.Lys537Ter)	TSPAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
254272	NM_017739.4(POMGNT1):c.466G>A (p.Glu156Lys)	TSPAN1	Pathogenic	no assertion criteria provided
3992	NM_017739.4(POMGNT1):c.1324C>T (p.Arg442Cys)	TSPAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
56587	NM_017739.4(POMGNT1):c.1769G>A (p.Trp590Ter)	TSPAN1	Pathogenic	criteria provided, multiple submitters, no conflicts
56589	NM_017739.4(POMGNT1):c.1814G>A (p.Arg605His)	TSPAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
56592	NM_017739.4(POMGNT1):c.1895+1G>A	TSPAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
56604	NM_017739.4(POMGNT1):c.643C>T (p.Arg215Ter)	TSPAN1	Pathogenic	criteria provided, multiple submitters, no conflicts
632108	NM_017739.4(POMGNT1):c.751+1G>A	TSPAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
642934	NM_017739.4(POMGNT1):c.652+1G>T	TSPAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
651215	NM_017739.4(POMGNT1):c.1001_1002del (p.Thr334fs)	TSPAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
862774	NM_017739.4(POMGNT1):c.1556del (p.Lys519fs)	TSPAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1802204	NM_017739.4(POMGNT1):c.1686T>A (p.Cys562Ter)	POMGNT1	Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 17 · 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
POMGNT1	Strong	Autosomal recessive	retinitis pigmentosa 76	17

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
POMGNT1	Orphanet:206564	POMGNT1-related limb-girdle muscular dystrophy R15
POMGNT1	Orphanet:370959	Congenital muscular dystrophy with cerebellar involvement
POMGNT1	Orphanet:588	Muscle-eye-brain disease
POMGNT1	Orphanet:791	Retinitis pigmentosa
POMGNT1	Orphanet:899	Walker-Warburg syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
POMGNT1	HGNC:19139	ENSG00000085998	Q8WZA1	Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1	gencc,clinvar
TSPAN1	HGNC:20657	ENSG00000117472	O60635	Tetraspanin-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
POMGNT1	Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1	Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins.
TSPAN1	Tetraspanin-1	Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
POMGNT1	Enzyme (other)	yes	2.4.1.312	Glyco_trans_13, Nucleotide-diphossugar_trans, POMGNT1_PANDER-like
TSPAN1	Other/Unknown	no		Tetraspanin_animals, Tetraspanin_EC2_sf, Tetraspanin/Peripherin

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
C1 segment of cervical spinal cord	1
adenohypophysis	1
apex of heart	1
bronchial epithelial cell	1
epithelium of bronchus	1
mucosa of transverse colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
POMGNT1	269	ubiquitous	marker	apex of heart, C1 segment of cervical spinal cord, adenohypophysis
TSPAN1	206	broad	marker	bronchial epithelial cell, epithelium of bronchus, mucosa of transverse colon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
POMGNT1	1,164
TSPAN1	949

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
POMGNT1	Q8WZA1	10

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TSPAN1	O60635	88.31

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 2 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
Defective POMGNT1 causes MDDGA3, MDDGB3 and MDDGC3	1	5710.0×	6e-04	POMGNT1
DAG1 core M1 glycosylations	1	2855.0×	6e-04	POMGNT1
DAG1 core M2 glycosylations	1	2284.0×	6e-04	POMGNT1
Matriglycan biosynthesis on DAG1	1	815.7×	0.001	POMGNT1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
localization of cell	1	1404.3×	0.005	POMGNT1
reactive gliosis	1	1203.7×	0.005	POMGNT1
protein O-linked glycosylation via mannose	1	468.1×	0.008	POMGNT1
dentate gyrus development	1	312.1×	0.008	POMGNT1
basement membrane organization	1	255.3×	0.008	POMGNT1
protein O-linked glycosylation via N-acetylgalactosamine	1	216.1×	0.008	POMGNT1
myelination	1	125.8×	0.012	POMGNT1
protein O-linked glycosylation	1	112.3×	0.012	POMGNT1
sensory perception of sound	1	50.5×	0.024	POMGNT1
gene expression	1	39.9×	0.027	POMGNT1
protein stabilization	1	33.4×	0.030	TSPAN1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
POMGNT1	0	0
TSPAN1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
POMGNT1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
POMGNT1	2.4.1.312	protein O-mannose beta-1,4-N-acetylglucosaminyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	1	POMGNT1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	TSPAN1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
POMGNT1	1	—
TSPAN1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.