autosomal recessive cutis laxa type 2D

Summary

autosomal recessive cutis laxa type 2D (MONDO:0027451) is a disease caused by ATP6V1A (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: ATP6V1A (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive cutis laxa type 2D
Mondo ID	MONDO:0027451
OMIM	617403
DOID	DOID:0070129
UMLS	C4479409
MedGen	1376619
GARD	0025498
Is cancer (heuristic)	no

Also known as: ARCL2D

Data availability: 8 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › autosomal recessive cutis laxa type 2 › autosomal recessive cutis laxa type 2D

Related subtypes (3): autosomal recessive cutis laxa type 2B, autosomal recessive cutis laxa type 2A, autosomal recessive cutis laxa type 2C

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

8 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
417773	NM_001690.4(ATP6V1A):c.215G>A (p.Gly72Asp)	ATP6V1A	Pathogenic	no assertion criteria provided
2627987	NM_001690.4(ATP6V1A):c.299A>T (p.Asp100Val)	ATP6V1A	Likely pathogenic	criteria provided, single submitter
3256729	NM_001690.4(ATP6V1A):c.841G>A (p.Gly281Arg)	ATP6V1A	Likely pathogenic	no assertion criteria provided
1986311	NM_001690.4(ATP6V1A):c.1798G>A (p.Asp600Asn)	ATP6V1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
417772	NM_001690.4(ATP6V1A):c.1012C>T (p.Arg338Cys)	ATP6V1A	Uncertain significance	criteria provided, multiple submitters, no conflicts
930734	NM_001690.4(ATP6V1A):c.1531G>C (p.Val511Leu)	ATP6V1A	Uncertain significance	criteria provided, single submitter
931142	NM_001690.4(ATP6V1A):c.1227-6A>G	ATP6V1A	Uncertain significance	criteria provided, single submitter
1584157	NM_001690.4(ATP6V1A):c.1291-7dup	ATP6V1A	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · 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
ATP6V1A	Strong	Autosomal recessive	autosomal recessive cutis laxa type 2D	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATP6V1A	Orphanet:357074	Autosomal recessive cutis laxa type 2, classic type
ATP6V1A	Orphanet:442835	Non-specific early-onset epileptic encephalopathy

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
ATP6V1A	HGNC:851	ENSG00000114573	P38606	V-type proton ATPase catalytic subunit A	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATP6V1A	V-type proton ATPase catalytic subunit A	Catalytic subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons.

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)
ATP6V1A	Other/Unknown	no		ATPase_F1/V1/A1_a/bsu_nucl-bd, ATPase_F1/V1/A1_a/bsu_N, ATPase_V1-cplx_asu

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
Brodmann (1909) area 23	1
endothelial cell	1
middle temporal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATP6V1A	300	ubiquitous	marker	Brodmann (1909) area 23, middle temporal gyrus, endothelial cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATP6V1A	3,301

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ATP6V1A	P38606	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autophagy	1	671.8×	0.004	ATP6V1A
Insulin receptor recycling	1	380.7×	0.004	ATP6V1A
Transferrin endocytosis and recycling	1	368.4×	0.004	ATP6V1A
ROS and RNS production in phagocytes	1	335.9×	0.004	ATP6V1A
Amino acids regulate mTORC1	1	200.3×	0.006	ATP6V1A
Ion channel transport	1	96.0×	0.010	ATP6V1A

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
cellular response to increased oxygen levels	1	2106.5×	0.002	ATP6V1A
Golgi lumen acidification	1	1685.2×	0.002	ATP6V1A
endosomal lumen acidification	1	1203.7×	0.002	ATP6V1A
intracellular pH reduction	1	1203.7×	0.002	ATP6V1A
synaptic vesicle lumen acidification	1	936.2×	0.002	ATP6V1A
vacuolar acidification	1	732.7×	0.002	ATP6V1A
lysosomal lumen acidification	1	674.1×	0.002	ATP6V1A
ATP metabolic process	1	468.1×	0.003	ATP6V1A
proton transmembrane transport	1	312.1×	0.004	ATP6V1A
regulation of macroautophagy	1	295.6×	0.004	ATP6V1A
intracellular iron ion homeostasis	1	244.2×	0.004	ATP6V1A

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
ATP6V1A	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ATP6V1A	2	Binding:2

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	ATP6V1A

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)
ATP6V1A	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.