arthrogryposis, distal, type 1C

Summary

arthrogryposis, distal, type 1C (MONDO:0030847) is a disease caused by MYL11 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: MYL11 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	arthrogryposis, distal, type 1C
Mondo ID	MONDO:0030847
OMIM	619110
DOID	DOID:0112190
UMLS	C5436834
MedGen	1722257
GARD	0016421
Is cancer (heuristic)	no

Also known as: arthrogryposis, distal, type 1C · DA1C

Data availability: 7 ClinVar variants · 6 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › distal arthrogryposis › arthrogryposis, distal, type 1C

Related subtypes (22): arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome, arthrogryposis-like hand anomaly-sensorineural deafness syndrome, Gordon syndrome, congenital contractural arachnodactyly, arthrogryposis, distal, type 2E, trismus-pseudocamptodactyly syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, Freeman-Sheldon syndrome, Sheldon-hall syndrome, Ehlers-Danlos syndrome, musculocontractural type, arthrogryposis-severe scoliosis syndrome, distal arthrogryposis type 5D, autism spectrum disorder - epilepsy - arthrogryposis syndrome, arthrogryposis, distal, with impaired proprioception and touch, digitotalar dysmorphism, distal arthrogryposis type 10, distal arthrogryposis Moore weaver type, arthrogryposis, distal, IIa 11, arthrogryposis-ectodermal dysplasia-other anomalies syndrome, ACTC1-related distal arthrogryposis with congenital heart disease, arthrogryposis, distal, type 2B4, arthrogryposis, distal, type 12

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

7 retrieved; paginated sample, class counts are floors:

4 pathogenic/likely pathogenic, 3 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
916685	NM_013292.5(MYL11):c.470G>T (p.Cys157Phe)	LOC112441444	Pathogenic/Likely pathogenic	no assertion criteria provided
916686	NM_013292.5(MYL11):c.469T>C (p.Cys157Arg)	LOC112441444	Pathogenic/Likely pathogenic	no assertion criteria provided
916687	NM_013292.5(MYL11):c.487G>A (p.Gly163Ser)	LOC112441444	Pathogenic/Likely pathogenic	no assertion criteria provided
916688	NM_013292.5(MYL11):c.98C>T (p.Ala33Val)	MYL11	Pathogenic/Likely pathogenic	no assertion criteria provided
2433958	NM_013292.5(MYL11):c.283_300dup (p.Ile100_Thr101insAspProGluAspValIle)	MYL11	Uncertain significance	criteria provided, single submitter
3237480	NM_013292.5(MYL11):c.74C>A (p.Thr25Asn)	MYL11	Uncertain significance	criteria provided, single submitter
3779996	NM_013292.5(MYL11):c.277+2T>C	MYL11	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
MYL11	Strong	Autosomal dominant	arthrogryposis, distal, type 1C	6

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
MYL11	HGNC:29824	ENSG00000180209	Q96A32	Myosin regulatory light chain 11	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYL11	Myosin regulatory light chain 11	Myosin regulatory subunit that plays an essential role to maintain muscle integrity during early development.

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)
MYL11	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS

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
biceps brachii	1
skeletal muscle tissue of biceps brachii	1
skeletal muscle tissue of rectus abdominis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYL11	184	broad	marker	biceps brachii, skeletal muscle tissue of biceps brachii, skeletal muscle tissue of rectus abdominis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYL11	2,170

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MYL11	Q96A32	84.43

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
Smooth Muscle Contraction	1	265.6×	0.008	MYL11
Muscle contraction	1	77.2×	0.013	MYL11

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
actin-myosin filament sliding	1	8426.0×	5e-04	MYL11
muscle tissue morphogenesis	1	2407.4×	8e-04	MYL11
skeletal muscle tissue development	1	290.6×	0.005	MYL11
muscle contraction	1	208.1×	0.005	MYL11

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
MYL11	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	MYL11

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)
MYL11	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.