Congenital muscular dystrophy due to integrin alpha-7 deficiency

Summary

Congenital muscular dystrophy due to integrin alpha-7 deficiency (MONDO:0013177) is a disease caused by ITGA7 (GenCC Strong), with 2 cohort genes and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Europe)
• Causal gene: ITGA7 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 953
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000	0.03	Europe	Not yet validated

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital muscular dystrophy due to integrin alpha-7 deficiency
Mondo ID	MONDO:0013177
MeSH	C567709
OMIM	613204
Orphanet	34520
DOID	DOID:0110639
UMLS	C2750786
MedGen	413044
GARD	0012587
Is cancer (heuristic)	no

Also known as: congenital muscular dystrophy caused by mutation in ITGA7 · congenital muscular dystrophy with integrin alpha-7 deficiency · congenital muscular dystrophy with ITGA7 deficiency · ITGA7 congenital muscular dystrophy · muscular dystrophy, congenital, due to ITGA7 deficiency

Data availability: 953 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 muscular dystrophy › congenital muscular dystrophy due to integrin alpha-7 deficiency

Related subtypes (22): Ullrich congenital muscular dystrophy, Bethlem myopathy, arthrogryposis due to muscular dystrophy, congenital muscular dystrophy-infantile cataract-hypogonadism syndrome, muscular dystrophy, congenital, with rapid progression, congenital myasthenic syndrome 10, megaconial type congenital muscular dystrophy, congenital muscular dystrophy 1B, congenital merosin-deficient muscular dystrophy 1A, congenital muscular dystrophy due to LMNA mutation, congenital muscular dystrophy-respiratory failure-skin abnormalities-joint hyperlaxity syndrome, congenital myopathy, Paradas type, autosomal recessive myogenic arthrogryposis multiplex congenita, muscular dystrophy-dystroglycanopathy, congenital muscular dystrophy with hyperlaxity, muscle-eye-brain disease, rigid spine syndrome, congenital muscular dystrophy with cataracts and intellectual disability, SNUPN-related muscular dystrophy with or without multi-system involvement, congenital muscular dystrophy caused by variation in POMGNT2, collagen 6-related congenital muscular dystrophy, congenital muscular dystrophy without intellectual disability

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

600 retrieved; paginated sample, class counts are floors:

263 likely benign, 255 uncertain significance, 16 pathogenic, 16 benign/likely benign, 16 benign, 14 conflicting classifications of pathogenicity, 12 likely pathogenic, 8 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1072319	NM_002206.3(ITGA7):c.517del (p.Arg173fs)	ITGA7	Pathogenic	criteria provided, single submitter
1076785	NM_002206.3(ITGA7):c.247C>T (p.Gln83Ter)	ITGA7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
129291	NM_002206.3(ITGA7):c.1088dup (p.His364fs)	ITGA7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324589	NM_002206.3(ITGA7):c.226C>T (p.Gln76Ter)	ITGA7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324590	NM_002206.3(ITGA7):c.1810C>T (p.Arg604Ter)	ITGA7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324591	NM_002206.3(ITGA7):c.1705C>T (p.Arg569Ter)	ITGA7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1394724	NM_002206.3(ITGA7):c.2331_2344del (p.Glu777fs)	ITGA7	Pathogenic	criteria provided, single submitter
1452654	NM_002206.3(ITGA7):c.34dup (p.Ala12fs)	ITGA7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1454083	NM_002206.3(ITGA7):c.445C>T (p.Arg149Ter)	ITGA7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1456806	NM_002206.3(ITGA7):c.187C>T (p.Gln63Ter)	ITGA7	Pathogenic	criteria provided, single submitter
1949025	NM_002206.3(ITGA7):c.2710del (p.Leu904fs)	ITGA7	Pathogenic	criteria provided, single submitter
2154907	NM_002206.3(ITGA7):c.2446C>T (p.Gln816Ter)	ITGA7	Pathogenic	criteria provided, single submitter
2415506	NM_002206.3(ITGA7):c.2670del (p.Gln891fs)	ITGA7	Pathogenic	criteria provided, single submitter
2424369	NC_000012.11:g.(?56091458)(56093230_?)del	ITGA7	Pathogenic	criteria provided, single submitter
2753782	NM_002206.3(ITGA7):c.1767del (p.Ile589fs)	ITGA7	Pathogenic	criteria provided, single submitter
2780776	NM_002206.3(ITGA7):c.2817del (p.Ala940fs)	ITGA7	Pathogenic	criteria provided, single submitter
2824329	NM_002206.3(ITGA7):c.2276del (p.Gln759fs)	ITGA7	Pathogenic	criteria provided, single submitter
2873714	NM_002206.3(ITGA7):c.2749dup (p.Glu917fs)	ITGA7	Pathogenic	criteria provided, single submitter
2891692	NM_002206.3(ITGA7):c.1966del (p.Thr656fs)	ITGA7	Pathogenic	criteria provided, single submitter
2911826	NM_002206.3(ITGA7):c.1327_1328del (p.Leu443fs)	ITGA7	Pathogenic	criteria provided, single submitter
2997928	NM_002206.3(ITGA7):c.2491C>T (p.Gln831Ter)	ITGA7	Pathogenic	criteria provided, single submitter
3242261	NM_002206.3(ITGA7):c.97_98insTG (p.Ala33fs)	ITGA7	Pathogenic	no assertion criteria provided
3607673	NM_002206.3(ITGA7):c.1068T>A (p.Tyr356Ter)	ITGA7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072841	NM_002206.3(ITGA7):c.2098C>T (p.Gln700Ter)	LOC126861535	Pathogenic	criteria provided, single submitter
1067219	NM_002206.3(ITGA7):c.334+1G>T	ITGA7	Likely pathogenic	criteria provided, single submitter
1324588	NM_002206.3(ITGA7):c.1825C>T (p.Gln609Ter)	ITGA7	Likely pathogenic	criteria provided, single submitter
1324594	NM_002206.3(ITGA7):c.1474C>T (p.Gln492Ter)	ITGA7	Likely pathogenic	criteria provided, single submitter
1324595	NM_002206.3(ITGA7):c.171_181del (p.Leu58fs)	ITGA7	Likely pathogenic	criteria provided, single submitter
1492330	NM_002206.3(ITGA7):c.670+1G>A	ITGA7	Likely pathogenic	criteria provided, single submitter
1496421	NM_002206.3(ITGA7):c.790+1G>A	ITGA7	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 6 · 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
ITGA7	Strong	Autosomal recessive	congenital muscular dystrophy due to integrin alpha-7 deficiency	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ITGA7	Orphanet:2020	Congenital fiber-type disproportion myopathy
ITGA7	Orphanet:34520	Congenital muscular dystrophy with integrin alpha-7 deficiency
CRPPA	Orphanet:352479	ISPD-related limb-girdle muscular dystrophy R20
CRPPA	Orphanet:370980	Congenital muscular dystrophy without intellectual disability
CRPPA	Orphanet:588	Muscle-eye-brain disease
CRPPA	Orphanet:899	Walker-Warburg syndrome

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
ITGA7	HGNC:6143	ENSG00000135424	Q13683	Integrin alpha-7	gencc,clinvar
CRPPA	HGNC:37276	ENSG00000214960	A4D126	D-ribitol-5-phosphate cytidylyltransferase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ITGA7	Integrin alpha-7	Integrin alpha-7/beta-1 is the primary laminin receptor on skeletal myoblasts and adult myofibers.
CRPPA	D-ribitol-5-phosphate cytidylyltransferase	Cytidylyltransferase required for protein O-linked mannosylation.

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
Antibody/Immunoglobulin	1	14.6×	0.135
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ITGA7	Antibody/Immunoglobulin	yes		Integrin_alpha, FG-GAP, Int_alpha_beta-p
CRPPA	Enzyme (other)	yes	2.7.7.40	ISPD_synthase_CS, Nucleotide-diphossugar_trans, IspD/TarI

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
apex of heart	1
descending thoracic aorta	1
right coronary artery	1
calcaneal tendon	1
corpus callosum	1
male germ line stem cell (sensu Vertebrata) in testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ITGA7	270	broad	marker	apex of heart, right coronary artery, descending thoracic aorta
CRPPA	134	ubiquitous	yes	corpus callosum, male germ line stem cell (sensu Vertebrata) in testis, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ITGA7	1,689
CRPPA	1,629

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CRPPA	A4D126	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ITGA7	Q13683	79.14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Matriglycan biosynthesis on DAG1	1	407.9×	0.012	CRPPA
Laminin interactions	1	190.3×	0.013	ITGA7
ECM proteoglycans	1	75.1×	0.019	ITGA7
Integrin cell surface interactions	1	67.2×	0.019	ITGA7
Extracellular matrix organization	1	31.6×	0.031	ITGA7

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
isoprenoid biosynthetic process	1	842.6×	0.009	CRPPA
protein O-linked glycosylation via mannose	1	468.1×	0.009	CRPPA
leukocyte migration	1	312.1×	0.009	ITGA7
heterotypic cell-cell adhesion	1	290.6×	0.009	ITGA7
endodermal cell differentiation	1	247.8×	0.009	ITGA7
muscle organ development	1	83.4×	0.017	ITGA7
cell-matrix adhesion	1	81.8×	0.017	ITGA7
integrin-mediated signaling pathway	1	80.2×	0.017	ITGA7
regulation of cell shape	1	61.5×	0.020	ITGA7
cell-cell adhesion	1	50.8×	0.022	ITGA7
axon guidance	1	45.3×	0.022	CRPPA

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
ITGA7	0	0
CRPPA	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CRPPA	2.7.7.40	D-ribitol-5-phosphate cytidylyltransferase

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

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	1	CRPPA
D	Druggable family + AlphaFold only, no drug	1	ITGA7
E	Difficult family or no structure, no drug	0

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
ITGA7	0	—
CRPPA	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01403402	Not specified	RECRUITING	Congenital Muscle Disease Study of Patient and Family Reported Medical Information