Retinitis pigmentosa 73

Summary

Retinitis pigmentosa 73 (MONDO:0014687) is a disease caused by HGSNAT (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: HGSNAT (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 1,057

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 73
Mondo ID	MONDO:0014687
OMIM	616544
DOID	DOID:0110389
UMLS	C4225287
MedGen	907690
GARD	0016135
Is cancer (heuristic)	no

Also known as: HGSNAT retinitis pigmentosa · retinitis pigmentosa 73 · retinitis pigmentosa caused by mutation in HGSNAT · retinitis pigmentosa type 73 · RP73

Data availability: 1,057 ClinVar variants · 4 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 73

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 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

600 retrieved; paginated sample, class counts are floors:

338 likely benign, 191 uncertain significance, 30 pathogenic, 16 conflicting classifications of pathogenicity, 12 likely pathogenic, 6 benign, 6 pathogenic/likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1069082	NM_152419.3(HGSNAT):c.1508dup (p.Leu504fs)	HGSNAT	Pathogenic	criteria provided, single submitter
1073137	NM_152419.3(HGSNAT):c.376G>T (p.Glu126Ter)	HGSNAT	Pathogenic	criteria provided, single submitter
1074147	NM_152419.3(HGSNAT):c.1348del (p.Asp450fs)	HGSNAT	Pathogenic	criteria provided, multiple submitters, no conflicts
1075807	NM_152419.3(HGSNAT):c.682_740del (p.Pro228fs)	HGSNAT	Pathogenic	criteria provided, single submitter
1076291	NM_152419.3(HGSNAT):c.884_885insTATTTTTTTTTATTTTTTTNNNNNNNNNNTGTTAGCCAGGATGGTCTCGATCTCCTGACCTCATGATCCACCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCGGATCTTCCATTTTTCT (p.Leu295_Ser296insIlePhePheTyrPhePheXaaXaaXaaXaaLeuAlaArgMetValSerIleSerTer)	HGSNAT	Pathogenic	criteria provided, single submitter
1076551	NM_152419.3(HGSNAT):c.133dup (p.Arg45fs)	HGSNAT	Pathogenic	criteria provided, single submitter
1076934	NM_152419.3(HGSNAT):c.1054_1055insATCAATTTCTAATGGGATTTCCAGAGTTGAAAAAGACAAATATTCAGCTTTAGGAAGCACAGTTGAGTCCTGAGCAGTACAAATAAAAATATAGGCTGGGCACAGTGGCTCACATGTGTAATCCCAGCACTTTCGGAGGCTGAGGTGGGTGGATTGCTGGAGTCCAGCAGTTTGAAAACAGCCTGAGCAACATGGCAAGACCCCATCTCTACAAAAAATACAACAATTATCCGGGCATGGTGGCACAAGCCCGTAGTCCCAGCTACTCAGGAAGCTGAGGTGGATCGCTTGAGCCCGGGAGGTGGAGGTTGCAGTGAGCCAAGATCACACCATTGCACTCCACACTGAATGACAGAGTGAGACTGTCTTAATAAAAAATATGAGTCAGCGTATAAGTTAAAAGGAGTTTTAAAAGATACTAATCCAAAAGAAGGCAGAAAAGGAGAAACATAATAGACTTACCAGCCCAATTTAAAAGTCAGGGATTATAAACATGAATTGAAGAAGTGAGACCCAGTTA (p.Leu352delinsTyrGlnPheLeuMetGlyPheProGluLeuLysLysThrAsnIleGlnLeuTer)	HGSNAT	Pathogenic	criteria provided, single submitter
1230	NM_152419.3(HGSNAT):c.493+1G>A	HGSNAT	Pathogenic	criteria provided, multiple submitters, no conflicts
1231	NM_152419.3(HGSNAT):c.1345dup (p.Asp449fs)	HGSNAT	Pathogenic	criteria provided, multiple submitters, no conflicts
1232	NM_152419.3(HGSNAT):c.848C>T (p.Pro283Leu)	HGSNAT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1235	NM_152419.3(HGSNAT):c.525dup (p.Val176fs)	HGSNAT	Pathogenic	criteria provided, multiple submitters, no conflicts
1236	NM_152419.3(HGSNAT):c.372-2A>G	HGSNAT	Pathogenic	criteria provided, multiple submitters, no conflicts
1238	NM_152419.3(HGSNAT):c.1553C>T (p.Ser518Phe)	HGSNAT	Pathogenic	criteria provided, single submitter
1352962	NM_152419.3(HGSNAT):c.719del (p.Leu240fs)	HGSNAT	Pathogenic	criteria provided, single submitter
1374201	NM_152419.3(HGSNAT):c.1323C>A (p.Tyr441Ter)	HGSNAT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1412507	NM_152419.3(HGSNAT):c.87_100dup (p.Gln34fs)	HGSNAT	Pathogenic	criteria provided, single submitter
1453420	NM_152419.3(HGSNAT):c.1245C>A (p.Cys415Ter)	HGSNAT	Pathogenic	criteria provided, single submitter
1453457	NM_152419.3(HGSNAT):c.1464+1del	HGSNAT	Pathogenic	criteria provided, single submitter
1453856	NM_152419.3(HGSNAT):c.781G>T (p.Gly261Ter)	HGSNAT	Pathogenic	criteria provided, single submitter
1455195	NM_152419.3(HGSNAT):c.1610del (p.Leu537fs)	HGSNAT	Pathogenic	criteria provided, single submitter
1458656	NC_000008.10:g.(?43024296)(43024405_?)del	HGSNAT	Pathogenic	criteria provided, single submitter
1458765	NM_152419.3(HGSNAT):c.1034_1049del (p.Ile345fs)	HGSNAT	Pathogenic	criteria provided, single submitter
1459479	NC_000008.10:g.(?42977230)(43002226_?)del	HGSNAT	Pathogenic	criteria provided, single submitter
1492894	NM_152419.3(HGSNAT):c.118+1G>A	HGSNAT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1502696	NM_152419.3(HGSNAT):c.1543-2A>G	HGSNAT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1977688	NM_152419.3(HGSNAT):c.1691dup (p.Leu566fs)	HGSNAT	Pathogenic	criteria provided, single submitter
1992944	NM_152419.3(HGSNAT):c.1139del (p.Cys380fs)	HGSNAT	Pathogenic	criteria provided, single submitter
2002352	NM_152419.3(HGSNAT):c.244C>T (p.Gln82Ter)	HGSNAT	Pathogenic	criteria provided, single submitter
2007566	NM_152419.3(HGSNAT):c.10del (p.Ala4fs)	HGSNAT	Pathogenic	criteria provided, single submitter
2018296	NM_152419.3(HGSNAT):c.959del (p.Leu320fs)	HGSNAT	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 2 · 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
HGSNAT	Strong	Autosomal recessive	retinitis pigmentosa 73	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HGSNAT	Orphanet:791	Retinitis pigmentosa
HGSNAT	Orphanet:79271	Sanfilippo syndrome type C

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
HGSNAT	HGNC:26527	ENSG00000165102	Q68CP4	Heparan-alpha-glucosaminide N-acetyltransferase	gencc,clinvar
FNTA	HGNC:3782	ENSG00000168522	P49354	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HGSNAT	Heparan-alpha-glucosaminide N-acetyltransferase	Lysosomal acetyltransferase that acetylates the non-reducing terminal alpha-glucosamine residue of intralysosomal heparin or heparan sulfate, converting it into a substrate for luminal alpha-N-acetyl glucosaminidase.
FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	Essential subunit of both the farnesyltransferase and the geranylgeranyltransferase complex.

Protein-family classification

Druggable: 2 · 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)	2	12.0×	0.007

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HGSNAT	Enzyme (other)	yes	2.3.1.78	HGSNAT_cat
FNTA	Enzyme (other)	yes	2.5.1.58	Prenyl_trans_a

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
cervix squamous epithelium	1
mucosa of stomach	1
right uterine tube	1
esophagus squamous epithelium	1
gingival epithelium	1
olfactory bulb	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HGSNAT	287	ubiquitous	marker	mucosa of stomach, right uterine tube, cervix squamous epithelium
FNTA	298	ubiquitous	marker	esophagus squamous epithelium, gingival epithelium, olfactory bulb

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FNTA	1,080
HGSNAT	863

Intra-cohort edges

A	B	Sources
FNTA	HGSNAT	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FNTA	P49354	14
HGSNAT	Q68CP4	12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
MPS IIIC - Sanfilippo syndrome C	1	5710.0×	0.001	HGSNAT
GBP-mediated host defense	1	519.1×	0.007	FNTA
HS-GAG degradation	1	248.3×	0.007	HGSNAT
Apoptotic cleavage of cellular proteins	1	237.9×	0.007	FNTA
RAS processing	1	237.9×	0.007	FNTA
Inactivation, recovery and regulation of the phototransduction cascade	1	158.6×	0.008	FNTA
Potential therapeutics for SARS	1	57.1×	0.020	FNTA
Neutrophil degranulation	1	11.5×	0.085	HGSNAT

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
peptide pheromone maturation	1	8426.0×	0.001	FNTA
protein farnesylation	1	2808.7×	0.002	FNTA
protein geranylgeranylation	1	1404.3×	0.002	FNTA
regulation of microtubule-based movement	1	1404.3×	0.002	FNTA
heparan sulfate proteoglycan catabolic process	1	936.2×	0.002	HGSNAT
skeletal muscle acetylcholine-gated channel clustering	1	936.2×	0.002	FNTA
positive regulation of skeletal muscle acetylcholine-gated channel clustering	1	936.2×	0.002	FNTA
lysosomal transport	1	351.1×	0.004	HGSNAT
protein complex oligomerization	1	337.0×	0.004	HGSNAT
positive regulation of Rac protein signal transduction	1	324.1×	0.004	FNTA
Rac protein signal transduction	1	280.9×	0.004	FNTA
transforming growth factor beta receptor signaling pathway	1	79.5×	0.013	FNTA

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
FNTA	CORTISONE ACETATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FNTA	6	4
HGSNAT	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CORTISONE ACETATE	4	FNTA
LONAFARNIB	4	FNTA
TIPIFARNIB	3	FNTA
L-778123 FREE BASE	1	FNTA
GGTI-2418	1	FNTA
BMS-214662	1	FNTA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
FNTA	513	Binding:438, Functional:75

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HGSNAT	2.3.1.78	heparan-alpha-glucosaminide N-acetyltransferase
FNTA	2.5.1.58, 2.5.1.59	protein farnesyltransferase, protein geranylgeranyltransferase type I

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
FNTA	513

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

6 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)
CORTISONE ACETATE	4	FNTA
LONAFARNIB	4	FNTA
TIPIFARNIB	3	FNTA
L-778123 FREE BASE	1	FNTA
GGTI-2418	1	FNTA
BMS-214662	1	FNTA

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	FNTA
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	HGSNAT
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
HGSNAT	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.