Neurodegeneration with brain iron accumulation 7

disease

On this page

Also known as NBIA7

Summary

Neurodegeneration with brain iron accumulation 7 (MONDO:0054763) is a disease with 1 cohort gene.

At a glance

Cohort genes: 1
ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	neurodegeneration with brain iron accumulation 7
Mondo ID	MONDO:0054763
OMIM	617916
UMLS	C4693583
MedGen	1647672
GARD	0025969
Is cancer (heuristic)	no

Also known as: NBIA7 · neurodegeneration with brain iron accumulation 7

Data availability: 6 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › mineral metabolism disease › iron metabolism disease › neurodegeneration with brain iron accumulation › neurodegeneration with brain iron accumulation 7

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

6 retrieved; paginated sample, class counts are floors:

2 benign/likely benign, 2 conflicting classifications of pathogenicity, 1 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
503503	NM_001286611.2(REPS1):c.232G>C (p.Val78Leu)	REPS1	Pathogenic	no assertion criteria provided
503504	NM_001286611.2(REPS1):c.338C>A (p.Ala113Glu)	REPS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
638402	NM_001286611.2(REPS1):c.1927G>A (p.Asp643Asn)	REPS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4813552	NM_001286611.2(REPS1):c.1603T>G (p.Ser535Ala)	REPS1	Uncertain significance	criteria provided, single submitter
1170016	NM_001286611.2(REPS1):c.1789C>T (p.Pro597Ser)	REPS1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
638403	NM_001286611.2(REPS1):c.2056C>T (p.Pro686Ser)	REPS1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · 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
REPS1	Limited	Unknown	neurodegeneration with brain iron accumulation 7	2

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
REPS1	HGNC:15578	ENSG00000135597	Q96D71	RalBP1-associated Eps domain-containing protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
REPS1	RalBP1-associated Eps domain-containing protein 1	May coordinate the cellular actions of activated EGF receptors and Ral-GTPases.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
REPS1	Other/Unknown	no		EH_dom, EF_hand_dom, EF-hand-dom_pair

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
parotid gland	1
right uterine tube	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
REPS1	258	ubiquitous	marker	ventricular zone, right uterine tube, parotid gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
REPS1	1,377

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
REPS1	Q96D71	57.83

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
Cargo recognition for clathrin-mediated endocytosis	1	104.8×	0.012	REPS1
Clathrin-mediated endocytosis	1	85.2×	0.012	REPS1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
endosomal transport	1	244.2×	0.008	REPS1
endocytosis	1	95.2×	0.011	REPS1

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
REPS1	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	REPS1

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)
REPS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: REPS1