Retinitis pigmentosa 79

disease

On this page

Also known as RP79

Summary

Retinitis pigmentosa 79 (MONDO:0044320) is a disease caused by HK1 (GenCC Strong), with 2 cohort genes.

At a glance

Causal gene: HK1 (GenCC Strong)
Cohort genes: 2
ClinVar variants: 17

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 79
Mondo ID	MONDO:0044320
OMIM	617460
DOID	DOID:0061108
UMLS	C4479526
MedGen	1386200
GARD	0016231
Is cancer (heuristic)	no

Also known as: retinitis pigmentosa 79 · RP79

Data availability: 17 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 79

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

17 retrieved; paginated sample, class counts are floors:

6 benign, 4 uncertain significance, 4 pathogenic/likely pathogenic, 2 benign/likely benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1700095	NM_000188.3(HK1):c.1240G>A (p.Gly414Arg)	HK1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
372693	NM_000188.3(HK1):c.1370C>T (p.Thr457Met)	HK1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
421007	NM_000188.3(HK1):c.1334C>T (p.Ser445Leu)	HK1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
424845	NM_000188.3(HK1):c.2539G>A (p.Glu847Lys)	HK1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2581721	NM_000188.3(HK1):c.613del (p.Ala205fs)	HK1	Likely pathogenic	no assertion criteria provided
1333598	NM_000188.3(HK1):c.1525G>A (p.Val509Ile)	HK1	Uncertain significance	criteria provided, single submitter
1687570	NM_000188.3(HK1):c.1298G>A (p.Arg433His)	HK1	Uncertain significance	criteria provided, multiple submitters, no conflicts
971751	NM_000188.3(HK1):c.1550G>A (p.Arg517Gln)	HK1	Uncertain significance	criteria provided, multiple submitters, no conflicts
994250	NM_000188.3(HK1):c.949G>A (p.Gly317Ser)	HK1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1285347	NM_001358263.1(HK1):c.75+23T>C	HK1	Benign	criteria provided, multiple submitters, no conflicts
1285348	NM_000188.3(HK1):c.1839+31G>A	HK1	Benign	criteria provided, multiple submitters, no conflicts
1285349	NM_000188.3(HK1):c.2219+27T>C	HK1	Benign	criteria provided, multiple submitters, no conflicts
255483	NM_000188.3(HK1):c.1443G>A (p.Lys481=)	HK1	Benign	criteria provided, multiple submitters, no conflicts
439787	NM_000188.3(HK1):c.78C>G (p.Leu26=)	HK1	Benign	criteria provided, multiple submitters, no conflicts
776515	NM_000188.3(HK1):c.1031+6T>C	HK1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
994062	NM_001358263.1(HK1):c.75+5174A>G	HK1	Benign	criteria provided, multiple submitters, no conflicts
994196	NM_001358263.1(HK1):c.53T>C (p.Leu18Pro)	HK1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 35 · 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
HK1	Strong	Autosomal dominant	retinitis pigmentosa 79	16
KCNA4	Strong	Autosomal dominant	retinitis pigmentosa 79	19

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HK1	Orphanet:90031	Non-spherocytic hemolytic anemia due to hexokinase deficiency
HK1	Orphanet:99953	Charcot-Marie-Tooth disease type 4G

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
HK1	HGNC:4922	ENSG00000156515	P19367	Hexokinase-1	gencc,clinvar
KCNA4	HGNC:6222	ENSG00000182255	P22459	Potassium voltage-gated channel subfamily A member 4	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HK1	Hexokinase-1	Catalyzes the phosphorylation of various hexoses, such as D-glucose, D-glucosamine, D-fructose, D-mannose and 2-deoxy-D-glucose, to hexose 6-phosphate (D-glucose 6-phosphate, D-glucosamine 6-phosphate, D-fructose 6-phosphate, D-mannose 6-p…
KCNA4	Potassium voltage-gated channel subfamily A member 4	Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes.

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
Ion channel	1	55.8×	0.036
Kinase	1	13.9×	0.071

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HK1	Kinase	yes	2.7.1.1	Hexokinase, Hexokinase_BS, Hexokinase_N
KCNA4	Ion channel	yes		BTB/POZ_dom, T1-type_BTB, K_chnl_volt-dep_Kv

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
cerebellar vermis	1
pharyngeal mucosa	1
pons	1
adrenal tissue	1
nucleus accumbens	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HK1	291	ubiquitous	marker	cerebellar vermis, pharyngeal mucosa, pons
KCNA4	142	broad	marker	adrenal tissue, nucleus accumbens, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KCNA4	2,311
HK1	2,298

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HK1	P19367	10

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KCNA4	P22459	70.48

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Defective HK1 causes hexokinase deficiency (HK deficiency)	1	5710.0×	0.001	HK1
Synthesis of GDP-mannose	1	951.7×	0.003	HK1
Glycolysis	1	142.8×	0.012	HK1
Voltage gated Potassium channels	1	121.5×	0.012	KCNA4
Potassium Channels	1	67.2×	0.018	KCNA4
Neuronal System	1	22.1×	0.045	KCNA4

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
obsolete GDP-mannose biosynthetic process from mannose	1	2808.7×	0.003	HK1
GDP-mannose biosynthetic process	1	1404.3×	0.003	HK1
obsolete establishment of protein localization to mitochondrion	1	1404.3×	0.003	HK1
maintenance of protein location in mitochondrion	1	1404.3×	0.003	HK1
mannose metabolic process	1	1053.2×	0.003	HK1
carbohydrate phosphorylation	1	1053.2×	0.003	HK1
glucose 6-phosphate metabolic process	1	648.1×	0.004	HK1
fructose 6-phosphate metabolic process	1	561.7×	0.004	HK1
positive regulation of cytokine production involved in immune response	1	495.6×	0.004	HK1
canonical glycolysis	1	351.1×	0.006	HK1
intracellular glucose homeostasis	1	290.6×	0.006	HK1
glycolytic process	1	191.5×	0.009	HK1
action potential	1	179.3×	0.009	KCNA4
positive regulation of interleukin-1 beta production	1	129.6×	0.010	HK1
glucose metabolic process	1	127.7×	0.010	HK1
potassium ion transport	1	95.8×	0.013	KCNA4
potassium ion transmembrane transport	1	68.0×	0.017	KCNA4
protein homooligomerization	1	61.1×	0.018	KCNA4
inflammatory response	1	18.9×	0.055	HK1
innate immune response	1	16.8×	0.059	HK1

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HK1	1	3
KCNA4	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
EBSELEN	3	HK1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
KCNA4	30	Binding:26, ADMET:2, Toxicity:1, Functional:1
HK1	12	Binding:9, Functional:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HK1	2.7.1.1	hexokinase

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

1 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)
EBSELEN	3	HK1

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	1	HK1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	KCNA4
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)
KCNA4	30	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: HK1, KCNA4