nystagmus 1, congenital, X-linked

Summary

nystagmus 1, congenital, X-linked (MONDO:0010693) is a disease caused by FRMD7 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: FRMD7 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 73

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	nystagmus 1, congenital, X-linked
Mondo ID	MONDO:0010693
MeSH	C537853
OMIM	310700
DOID	DOID:0111790
UMLS	C1839580
MedGen	333352
GARD	0027796
Is cancer (heuristic)	no

Also known as: congenital nystagmus caused by mutation in FRMD7 · FRMD7 congenital nystagmus · NYS1 · Nystagmus 1, congenital, X- linked · nystagmus 1, congenital, X-linked · Nystagmus, infantile idiopathic

Data availability: 73 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › congenital nystagmus › nystagmus 1, congenital, X-linked

Related subtypes (9): nystagmus 2, congenital, autosomal dominant, nystagmus, hereditary vertical, spinocerebellar ataxia 27A, nystagmus, congenital, autosomal recessive, nystagmus 5, congenital, X-linked, nystagmus 6, congenital, X-linked, nystagmus, myoclonic, nystagmus 3, congenital, autosomal dominant, nystagmus 7, congenital, autosomal dominant

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

73 retrieved; paginated sample, class counts are floors:

21 uncertain significance, 15 pathogenic, 12 benign, 11 conflicting classifications of pathogenicity, 6 likely pathogenic, 4 likely benign, 3 pathogenic/likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1025022	NM_194277.3(FRMD7):c.580G>A (p.Ala194Thr)	FRMD7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
10782	NM_194277.3(FRMD7):c.601C>T (p.Gln201Ter)	FRMD7	Pathogenic	no assertion criteria provided
10783	NM_194277.3(FRMD7):c.1003C>T (p.Arg335Ter)	FRMD7	Pathogenic	criteria provided, multiple submitters, no conflicts
10784	NM_194277.3(FRMD7):c.205+2T>G	FRMD7	Pathogenic	no assertion criteria provided
10785	NM_194277.3(FRMD7):c.252G>A (p.Val84=)	FRMD7	Pathogenic	no assertion criteria provided
10786	NM_194277.3(FRMD7):c.70G>A (p.Gly24Arg)	FRMD7	Pathogenic	criteria provided, multiple submitters, no conflicts
10787	NM_194277.3(FRMD7):c.38AGA[1] (p.Lys14del)	FRMD7	Pathogenic	no assertion criteria provided
10788	NM_194277.3(FRMD7):c.425T>G (p.Leu142Arg)	FRMD7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
10789	NM_194277.3(FRMD7):c.685C>G (p.Arg229Gly)	FRMD7	Pathogenic	no assertion criteria provided
10790	NM_194277.3(FRMD7):c.1275_1276del (p.Glu426fs)	FRMD7	Pathogenic	no assertion criteria provided
1197628	NM_194277.3(FRMD7):c.782G>A (p.Arg261Gln)	FRMD7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
192295	NM_194277.3(FRMD7):c.556A>G (p.Met186Val)	FRMD7	Pathogenic	criteria provided, single submitter
2737370	NM_194277.3(FRMD7):c.910C>T (p.Arg304Ter)	FRMD7	Pathogenic	criteria provided, multiple submitters, no conflicts
29976	NM_194277.3(FRMD7):c.691T>G (p.Leu231Val)	FRMD7	Pathogenic	criteria provided, single submitter
29977	NM_194277.3(FRMD7):c.812G>A (p.Cys271Tyr)	FRMD7	Pathogenic	no assertion criteria provided
29978	NM_194277.3(FRMD7):c.1050+5G>A	FRMD7	Pathogenic	no assertion criteria provided
625800	GRCh37/hg19 Xq26.1-26.2(chrX:130280298-132670366)	FRMD7	Pathogenic	criteria provided, single submitter
987019	NM_194277.3(FRMD7):c.781C>T (p.Arg261Ter)	FRMD7	Pathogenic	criteria provided, multiple submitters, no conflicts
1710201	NM_194277.3(FRMD7):c.832T>C (p.Phe278Leu)	FRMD7	Likely pathogenic	no assertion criteria provided
2428834	NM_194277.3(FRMD7):c.902A>G (p.Tyr301Cys)	FRMD7	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3776258	NM_194277.3(FRMD7):c.1777C>T (p.Gln593Ter)	FRMD7	Likely pathogenic	criteria provided, single submitter
4087725	NM_194277.3(FRMD7):c.799T>G (p.Phe267Val)	FRMD7	Likely pathogenic	criteria provided, single submitter
4681184	NM_194277.3(FRMD7):c.162+1G>A	FRMD7	Likely pathogenic	criteria provided, single submitter
976097	NM_194277.3(FRMD7):c.1050+1G>C	FRMD7	Likely pathogenic	criteria provided, single submitter
1324432	NM_194277.3(FRMD7):c.875T>C (p.Leu292Pro)	FRMD7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2091793	NM_194277.3(FRMD7):c.595G>T (p.Gly199Trp)	FRMD7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2152352	NM_194277.3(FRMD7):c.886G>T (p.Gly296Cys)	FRMD7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
367907	NM_194277.3(FRMD7):c.1643A>C (p.Gln548Pro)	FRMD7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
367910	NM_194277.3(FRMD7):c.458G>A (p.Cys153Tyr)	FRMD7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
712417	NM_194277.3(FRMD7):c.1588C>T (p.Pro530Ser)	FRMD7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
FRMD7	Definitive	X-linked	nystagmus 1, congenital, X-linked	4

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
FRMD7	HGNC:8079	ENSG00000165694	Q6ZUT3	FERM domain-containing protein 7	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FRMD7	FERM domain-containing protein 7	Plays a role in neurite development, may be through the activation of the GTPase RAC1.

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)
FRMD7	Other/Unknown	no		FERM_domain, PH-like_dom_sf, FERM/acyl-CoA-bd_prot_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
calcaneal tendon	1
cartilage tissue	1
tendon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FRMD7	54		marker	calcaneal tendon, tendon, cartilage tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FRMD7	687

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FRMD7	Q6ZUT3	62.31

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
positive regulation of small GTPase mediated signal transduction	1	2106.5×	0.002	FRMD7
positive regulation of lamellipodium assembly	1	601.9×	0.003	FRMD7
negative regulation of stress fiber assembly	1	581.1×	0.003	FRMD7
regulation of neuron projection development	1	432.1×	0.003	FRMD7
nervous system development	1	45.9×	0.022	FRMD7

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
FRMD7	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	FRMD7

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)
FRMD7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.