Congenital muscular dystrophy with cataracts and intellectual disability

Summary

Congenital muscular dystrophy with cataracts and intellectual disability (MONDO:0024607) is a disease caused by INPP5K (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: INPP5K (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 29
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		23	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital muscular dystrophy with cataracts and intellectual disability
Mondo ID	MONDO:0024607
OMIM	617404
Orphanet	662184
DOID	DOID:0080197
UMLS	C4479410
MedGen	1382291
GARD	0025435
Is cancer (heuristic)	no

Also known as: MDCCAID

Data availability: 29 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 with cataracts and intellectual disability

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 integrin alpha-7 deficiency, 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, 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

29 retrieved; paginated sample, class counts are floors:

13 uncertain significance, 7 pathogenic, 4 conflicting classifications of pathogenicity, 3 likely pathogenic, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1710311	NM_016532.4(INPP5K):c.165G>T (p.Leu55Phe)	INPP5K	Pathogenic	no assertion criteria provided
1710312	NM_016532.4(INPP5K):c.753_756del (p.Arg251fs)	INPP5K	Pathogenic	no assertion criteria provided
417778	NM_016532.4(INPP5K):c.899A>G (p.Tyr300Cys)	INPP5K	Pathogenic	no assertion criteria provided
417779	NM_016532.4(INPP5K):c.277A>G (p.Met93Val)	INPP5K	Pathogenic	no assertion criteria provided
417780	NM_016532.4(INPP5K):c.67G>A (p.Val23Met)	INPP5K	Pathogenic	criteria provided, single submitter
417781	NM_016532.4(INPP5K):c.805G>A (p.Asp269Asn)	INPP5K	Pathogenic	no assertion criteria provided
417782	NM_016532.4(INPP5K):c.1251_1252del (p.Asn417fs)	INPP5K	Pathogenic	no assertion criteria provided
1708251	NM_016532.4(INPP5K):c.653G>A (p.Trp218Ter)	INPP5K	Likely pathogenic	criteria provided, single submitter
1708252	NM_016532.4(INPP5K):c.925A>G (p.Ser309Gly)	INPP5K	Likely pathogenic	criteria provided, single submitter
417783	NM_016532.4(INPP5K):c.418G>A (p.Gly140Ser)	INPP5K	Likely pathogenic	criteria provided, single submitter
1029611	NM_016532.4(INPP5K):c.302T>C (p.Phe101Ser)	INPP5K	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
417777	NM_016532.4(INPP5K):c.149T>C (p.Ile50Thr)	INPP5K	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
715884	NM_016532.4(INPP5K):c.119A>G (p.Asn40Ser)	INPP5K	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
729199	NM_016532.4(INPP5K):c.427G>A (p.Val143Ile)	INPP5K	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1333525	NM_016532.4(INPP5K):c.793C>T (p.Pro265Ser)	INPP5K	Uncertain significance	criteria provided, single submitter
1333698	NM_016532.4(INPP5K):c.419G>A (p.Gly140Asp)	INPP5K	Uncertain significance	criteria provided, single submitter
1710488	NM_016532.4(INPP5K):c.1247G>C (p.Ser416Thr)	INPP5K	Uncertain significance	criteria provided, single submitter
1799519	NM_016532.4(INPP5K):c.809G>A (p.Arg270His)	INPP5K	Uncertain significance	criteria provided, single submitter
1799521	NM_016532.4(INPP5K):c.152+5G>T	INPP5K	Uncertain significance	criteria provided, single submitter
2401745	NM_016532.4(INPP5K):c.850G>A (p.Asp284Asn)	INPP5K	Uncertain significance	criteria provided, multiple submitters, no conflicts
2689249	NM_016532.4(INPP5K):c.32G>A (p.Gly11Asp)	INPP5K	Uncertain significance	criteria provided, single submitter
3529232	NM_016532.4(INPP5K):c.853A>G (p.Thr285Ala)	INPP5K	Uncertain significance	criteria provided, multiple submitters, no conflicts
4079003	NM_016532.4(INPP5K):c.1259G>A (p.Arg420His)	INPP5K	Uncertain significance	criteria provided, single submitter
4079004	NM_016532.4(INPP5K):c.606G>T (p.Leu202Phe)	INPP5K	Uncertain significance	criteria provided, single submitter
4079005	NM_016532.4(INPP5K):c.1323G>A (p.Leu441=)	INPP5K	Uncertain significance	criteria provided, single submitter
4079006	NM_016532.4(INPP5K):c.980C>G (p.Ser327Cys)	INPP5K	Uncertain significance	criteria provided, single submitter
4079007	NM_016532.4(INPP5K):c.394G>A (p.Val132Ile)	INPP5K	Uncertain significance	criteria provided, single submitter
1185400	NM_016532.4(INPP5K):c.554+16del	INPP5K	Benign	criteria provided, multiple submitters, no conflicts
1185401	NM_016532.4(INPP5K):c.-60G>T	INPP5K	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
INPP5K	Strong	Autosomal recessive	congenital muscular dystrophy with cataracts and intellectual disability	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
INPP5K	Orphanet:662184	Congenital muscular dystrophy-cataract-intellectual disability syndrome

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
INPP5K	HGNC:33882	ENSG00000132376	Q9BT40	Inositol polyphosphate 5-phosphatase K	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
INPP5K	Inositol polyphosphate 5-phosphatase K	Inositol 5-phosphatase which acts on inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate, phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate.

Protein-family classification

Druggable: 1 · 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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
INPP5K	Enzyme (other)	yes	3.1.3.56	IPPc, Endo/exonu/phosph_ase_sf, SKICH

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
pigmented layer of retina	1
right lobe of thyroid gland	1
right lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
INPP5K	283	ubiquitous	marker	pigmented layer of retina, right lung, right lobe of thyroid gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
INPP5K	1,300

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
INPP5K	Q9BT40	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
PI Metabolism	1	356.9×	0.008	INPP5K
Synthesis of PIPs at the plasma membrane	1	211.5×	0.008	INPP5K
Phospholipid metabolism	1	200.3×	0.008	INPP5K
Metabolism of lipids	1	31.6×	0.040	INPP5K
Metabolism	1	11.6×	0.086	INPP5K

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 renal water transport	1	16852.0×	0.002	INPP5K
negative regulation of dephosphorylation	1	4213.0×	0.002	INPP5K
negative regulation of D-glucose transmembrane transport	1	3370.4×	0.002	INPP5K
negative regulation of protein targeting to membrane	1	2808.7×	0.002	INPP5K
negative regulation of glycogen biosynthetic process	1	2106.5×	0.002	INPP5K
regulation of glycogen biosynthetic process	1	1872.4×	0.002	INPP5K
negative regulation of calcium ion transport	1	1685.2×	0.002	INPP5K
negative regulation of single stranded viral RNA replication via double stranded DNA intermediate	1	1532.0×	0.002	INPP5K
positive regulation of urine volume	1	1296.3×	0.002	INPP5K
host-mediated suppression of viral transcription	1	1296.3×	0.002	INPP5K
ruffle assembly	1	1296.3×	0.002	INPP5K
phosphatidylinositol dephosphorylation	1	648.1×	0.004	INPP5K
negative regulation of stress fiber assembly	1	581.1×	0.004	INPP5K
cellular response to hormone stimulus	1	383.0×	0.005	INPP5K
negative regulation of insulin receptor signaling pathway	1	374.5×	0.005	INPP5K
phosphatidylinositol biosynthetic process	1	366.4×	0.005	INPP5K
cellular response to epidermal growth factor stimulus	1	318.0×	0.005	INPP5K
cellular response to cAMP	1	290.6×	0.005	INPP5K
negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	263.3×	0.006	INPP5K
cellular response to insulin stimulus	1	170.2×	0.008	INPP5K
cellular response to tumor necrosis factor	1	163.6×	0.008	INPP5K
glucose homeostasis	1	130.6×	0.010	INPP5K
protein localization to plasma membrane	1	108.7×	0.011	INPP5K
actin cytoskeleton organization	1	79.1×	0.015	INPP5K
in utero embryonic development	1	72.0×	0.016	INPP5K
G protein-coupled receptor signaling pathway	1	36.2×	0.030	INPP5K
negative regulation of DNA-templated transcription	1	31.6×	0.033	INPP5K
positive regulation of DNA-templated transcription	1	27.9×	0.036	INPP5K

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
INPP5K	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
INPP5K	3.1.3.56	inositol-polyphosphate 5-phosphatase

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	1	INPP5K
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
INPP5K	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