Myofibrillar myopathy 7

Summary

Myofibrillar myopathy 7 (MONDO:0014922) is a disease caused by KY (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: KY (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 27

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myofibrillar myopathy 7
Mondo ID	MONDO:0014922
OMIM	617114
DOID	DOID:0080098
UMLS	C4310711
MedGen	934678
GARD	0025034
Is cancer (heuristic)	no

Also known as: KY myofibrillar myopathy (disease) · MFM7 · myofibrillar myopathy (disease) caused by mutation in KY · myopathy, myofibrillar, 7 · myopathy, myofibrillar, type 7

Data availability: 27 ClinVar variants · 3 GenCC gene-disease records.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › myofibrillar myopathy 7

Related subtypes (216): polymicrogyria, congenital myasthenic syndrome with tubular aggregates, prenatal-onset spinal muscular atrophy with congenital bone fractures, anencephaly, cerebral cavernous malformation, meningocele, progressive external ophthalmoplegia, congenital nystagmus, congenital toxoplasmosis, congenital contractural arachnodactyly, congenital trigeminal anesthesia, familial congenital palsy of trochlear nerve, Myhre syndrome, Aase-Smith syndrome, KBG syndrome, autosomal dominant primary microcephaly, Mobius syndrome, MYH7-related skeletal myopathy, congenital stationary night blindness autosomal dominant 2, Prader-Willi syndrome, congenital myopathy 7A, myosin storage, autosomal dominant, Smith-Magenis syndrome, spina bifida, Freeman-Sheldon syndrome, isolated cerebellar hypoplasia/agenesis, Chediak-Higashi syndrome, Cohen syndrome, multiple pterygium-malignant hyperthermia syndrome, corpus callosum, agenesis of, congenital lactic acidosis, Saguenay-Lac-Saint-Jean type, facial dysmorphism-macrocephaly-myopia-Dandy-Walker malformation syndrome, diastematomyelia, EEM syndrome, Mowat-Wilson syndrome, Johanson-Blizzard syndrome, intellectual disability, Buenos-Aires type, myasthenia, congenital, refractory to acetylcholinesterase inhibitors, congenital myasthenic syndrome 6, Bailey-Bloch congenital myopathy, congenital stationary night blindness 1B, radioulnar synostosis-developmental delay-hypotonia syndrome, Schinzel-Giedion syndrome, schizencephaly, intellectual disability, Wolff type, X-linked intellectual disability-plagiocephaly syndrome, X-linked adrenal hypoplasia congenita, syndromic X-linked intellectual disability 7, syndromic X-linked intellectual disability Shashi type, syndromic X-linked intellectual disability Lubs type, syndromic X-linked intellectual disability Abidi type, syndromic X-linked intellectual disability Siderius type, X-linked intellectual disability, Cabezas type, X-linked intellectual disability-cubitus valgus-dysmorphism syndrome, syndromic X-linked intellectual disability Claes-Jensen type, moyamoya angiopathy-short stature-facial dysmorphism-hypergonadotropic hypogonadism syndrome, multiple congenital anomalies-hypotonia-seizures syndrome 2, developmental and epileptic encephalopathy, 36, blepharophimosis - intellectual disability syndrome, MKB type, X-linked intellectual disability-short stature-overweight syndrome, intellectual disability, X-linked, syndromic 33, syndromic X-linked intellectual disability 34, infantile-onset X-linked spinal muscular atrophy, syndromic X-linked intellectual disability 5, holoprosencephaly-hypokinesia-congenital contractures syndrome, X-linked intellectual disability with marfanoid habitus, Wieacker-Wolff syndrome, MERRF syndrome, macrocephaly-spastic paraplegia-dysmorphism syndrome, intellectual disability-sparse hair-brachydactyly syndrome, myofibrillar myopathy 1, isolated hereditary congenital facial paralysis, fibrosis of extraocular muscles, congenital, 2, Pierpont syndrome, congenital cataracts-facial dysmorphism-neuropathy syndrome, Bohring-Opitz syndrome, PHACE syndrome, B4GALT1-congenital disorder of glycosylation, developmental malformations-deafness-dystonia syndrome, sensory ataxic neuropathy, dysarthria, and ophthalmoparesis, AICA-ribosiduria, myofibrillar myopathy 3, fibrosis of extraocular muscles, congenital, 3c, myofibrillar myopathy 4, myofibrillar myopathy 5, cone-rod synaptic disorder, congenital nonprogressive, congenital stationary night blindness autosomal dominant 3, congenital stationary night blindness autosomal dominant 1, intellectual disability, autosomal recessive 12, progressive myoclonic epilepsy type 3, chromosome 15q13.3 microdeletion syndrome, combined pituitary hormone deficiencies, genetic form, congenital stationary night blindness 1D, DYRK1A-related intellectual disability syndrome, Pitt-Hopkins-like syndrome 2, developmental and epileptic encephalopathy, 15, Schuurs-Hoeijmakers syndrome, severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome, severe intellectual disability-progressive spastic diplegia syndrome, hypotonia, infantile, with psychomotor retardation and characteristic facies, developmental and epileptic encephalopathy, 18, CTCF-related neurodevelopmental disorder, autism spectrum disorder due to AUTS2 deficiency, developmental and epileptic encephalopathy, 23, ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder, Bardet-Biedl syndrome 11, cerebellar-facial-dental syndrome, fibrosis of extraocular muscles, congenital, 5, congenital myasthenic syndrome 15, lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome, autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome, congenital myasthenic syndrome 18, autosomal recessive spinocerebellar ataxia 20, Houge-Janssens syndrome 1, intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome, congenital stationary night blindness 1G, hypomyelinating leukodystrophy 10, developmental and epileptic encephalopathy, 50, congenital insensitivity to pain-hypohidrosis syndrome, macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome, SLC39A8-CDG, spastic paraplegia-severe developmental delay-epilepsy syndrome, cardiac anomalies - developmental delay - facial dysmorphism syndrome, severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome, intellectual disability, autosomal recessive 53, TELO2-related intellectual disability-neurodevelopmental disorder, micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome, autosomal recessive limb-girdle muscular dystrophy type 2Y, short stature-brachydactyly-obesity-global developmental delay syndrome, autosomal recessive limb-girdle muscular dystrophy type 2R1, severe microbrachycephaly-intellectual disability-athetoid cerebral palsy syndrome, congenital laryngeal palsy, congenital or early infantile CACH syndrome, congenital epulis, severe congenital nemaline myopathy, intermediate nemaline myopathy, typical nemaline myopathy, childhood-onset nemaline myopathy, adult-onset nemaline myopathy, qualitative or quantitative defects of protein involved in O-glycosylation of alpha-dystroglycan, holoprosencephaly, congenital insensitivity to pain with hyperhidrosis, congenital hydrocephalus, familial congenital mirror movements, macrocephaly-short stature-paraplegia syndrome, cephalocele, mitochondrial neurogastrointestinal encephalomyopathy, X-linked intellectual disability-hypogonadism-ichthyosis-obesity-short stature syndrome, 7p22.1 microduplication syndrome, congenital achiasma, congenital retinal arteriovenous communication, 3q27.3 microdeletion syndrome, Prader-Willi-like syndrome, 9q31.1q31.3 microdeletion syndrome, congenital oculomotor nerve palsy, congenital abducens nerve palsy, neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome, congenital insensitivity to pain with severe intellectual disability, X-linked intellectual disability-cerebellar hypoplasia-spondylo-epiphyseal dysplasia syndrome, global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome, lissencephaly spectrum disorders, hyaline body myopathy, 22q11.2 deletion syndrome, craniorachischisis, Leber congenital amaurosis, Ritscher-Schinzel syndrome, Rubinstein-Taybi syndrome, X-linked intellectual disability-hypogammaglobulinemia-progressive neurological deterioration syndrome, X-linked intellectual disability-epilepsy-progressive joint contractures-dysmorphism syndrome, X-linked intellectual disability, Pai type, X-linked intellectual disability, Stevenson type, X-linked intellectual disability, Stoll type, congenital muscular dystrophy, congenital vitreoretinal dysplasia, periventricular nodular heterotopia, postsynaptic congenital myasthenic syndrome, subcortical band heterotopia, congenital fibrosis of extraocular muscles type 1, Al Gazali Khidr Prem Chandran syndrome, distal arthrogryposis Moore weaver type, congenital myotonic dystrophy, myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive, intellectual disability, autosomal dominant 47, intellectual disability, autosomal dominant 48, spondyloepiphyseal dysplasia, sensorineural hearing loss, impaired intellectual development, and leber congenital amaurosis, myasthenic syndrome, congenital, 23, presynaptic, myasthenic syndrome, congenital, 24, presynaptic, myasthenic syndrome, congenital, 25, presynaptic, developmental and epileptic encephalopathy, 77, night blindness, congenital stationary, type1i, neuropathy, congenital hypomelinating, congenital axonal neuropathy with encephalopathy, developmental and epileptic encephalopathy, 73, PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome, isolated exencephaly, myasthenic syndrome, congenital, 22, intellectual developmental disorder with gastrointestinal difficulties and high pain threshold, intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, 9q33.3q34.11 microdeletion syndrome, congenital labioscrotal agenesis-cerebellar malformation-corneal dystrophy-facial dysmorphism syndrome, early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome, SIN3A-related intellectual disability syndrome, childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder, X-linked congenital stationary night blindness, neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, FOXG1 disorder, alpha-actinopathy, TPM3-related myopathy, X-linked recessive mitochondrial myopathy, RYR1-related myopathy, TTN-related myopathy, TPM2-related myopathy, myopathy caused by variation in POMGNT1, central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, segmental spinal dysgenesis, myopathy, myofibrillar, 13, with rimmed vacuoles, congenital neuronal ceroid lipofuscinosis 10

Subtypes (1): kyphosis-lateral tongue atrophy-myofibrillar myopathy syndrome

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

27 retrieved; paginated sample, class counts are floors:

14 uncertain significance, 4 benign, 4 likely pathogenic, 4 pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
254181	NM_178554.6(KY):c.405C>A (p.Tyr135Ter)	CEP63	Pathogenic	no assertion criteria provided
2581449	NM_178554.6(KY):c.481C>T (p.Gln161Ter)	CEP63	Pathogenic	criteria provided, single submitter
997854	NM_178554.6(KY):c.415C>T (p.Arg139Ter)	CEP63	Pathogenic	no assertion criteria provided
254182	NM_178554.6(KY):c.1071del (p.Thr358fs)	KY	Pathogenic	no assertion criteria provided
1339572	NM_178554.6(KY):c.1247T>A (p.Ile416Asn)	CEP63	Likely pathogenic	no assertion criteria provided
2441032	NM_178554.6(KY):c.76del (p.Ala26fs)	CEP63	Likely pathogenic	criteria provided, single submitter
3896971	NM_178554.6(KY):c.408del (p.Trp137fs)	CEP63	Likely pathogenic	criteria provided, single submitter
4849338	NM_178554.6(KY):c.642del (p.Thr215fs)	CEP63	Likely pathogenic	criteria provided, single submitter
74875	NM_178554.6(KY):c.508G>A (p.Glu170Lys)	CEP63	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1031310	NM_178554.6(KY):c.884C>G (p.Ser295Cys)	CEP63	Uncertain significance	criteria provided, multiple submitters, no conflicts
1032559	NM_178554.6(KY):c.1901G>T (p.Cys634Phe)	CEP63	Uncertain significance	criteria provided, multiple submitters, no conflicts
1698336	NM_178554.6(KY):c.373C>T (p.Arg125Trp)	CEP63	Uncertain significance	criteria provided, multiple submitters, no conflicts
2365840	NM_178554.6(KY):c.602T>C (p.Ile201Thr)	CEP63	Uncertain significance	criteria provided, multiple submitters, no conflicts
2433274	NM_178554.6(KY):c.21C>G (p.Ile7Met)	CEP63	Uncertain significance	criteria provided, single submitter
2574870	NM_178554.6(KY):c.560G>A (p.Arg187His)	CEP63	Uncertain significance	criteria provided, multiple submitters, no conflicts
2689338	NM_178554.6(KY):c.1895C>G (p.Ala632Gly)	CEP63	Uncertain significance	criteria provided, multiple submitters, no conflicts
3064685	NM_178554.6(KY):c.337+5G>T	CEP63	Uncertain significance	criteria provided, single submitter
3536676	NM_178554.6(KY):c.1496A>G (p.Asp499Gly)	CEP63	Uncertain significance	criteria provided, multiple submitters, no conflicts
3536677	NM_178554.6(KY):c.1354G>A (p.Val452Met)	CEP63	Uncertain significance	criteria provided, multiple submitters, no conflicts
4079149	NM_178554.6(KY):c.1052T>G (p.Met351Arg)	CEP63	Uncertain significance	criteria provided, single submitter
4079150	NM_178554.6(KY):c.1969A>G (p.Lys657Glu)	CEP63	Uncertain significance	criteria provided, multiple submitters, no conflicts
4079151	NM_178554.6(KY):c.1432G>A (p.Gly478Arg)	CEP63	Uncertain significance	criteria provided, single submitter
4079152	NM_178554.6(KY):c.1694G>A (p.Trp565Ter)	CEP63	Uncertain significance	criteria provided, single submitter
1175657	NM_178554.6(KY):c.1251T>C (p.Phe417=)	CEP63	Benign	criteria provided, multiple submitters, no conflicts
1183341	NM_178554.6(KY):c.87G>T (p.Thr29=)	CEP63	Benign	criteria provided, multiple submitters, no conflicts
1251525	NM_178554.6(KY):c.1593C>G (p.Gly531=)	KY	Benign	criteria provided, multiple submitters, no conflicts
1289017	NM_178554.6(KY):c.1665T>C (p.Leu555=)	KY	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 3 · 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
KY	Strong	Autosomal recessive	myofibrillar myopathy 7	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KY	Orphanet:496686	Kyphosis-lateral tongue atrophy-myofibrillar myopathy syndrome
KY	Orphanet:496689	Kyphoscoliosis-lateral tongue atrophy-hereditary spastic paraplegia syndrome
CEP63	Orphanet:808	Seckel 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
KY	HGNC:26576	ENSG00000174611	Q8NBH2	Kyphoscoliosis peptidase	gencc,clinvar
CEP63	HGNC:25815	ENSG00000182923	Q96MT8	Centrosomal protein of 63 kDa	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KY	Kyphoscoliosis peptidase	Probable cytoskeleton-associated protease required for normal muscle growth.
CEP63	Centrosomal protein of 63 kDa	Required for normal spindle assembly.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KY	Antibody/Immunoglobulin	yes		Transglutaminase-like, Papain-like_cys_pep_sf, CAP/Cytokinesis_protein
CEP63	Other/Unknown	no		CEP63/Deup1_N, CEP63/Deup1_CC

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
body of tongue	1
quadriceps femoris	1
vastus lateralis	1
calcaneal tendon	1
colonic epithelium	1
cortical plate	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KY	184	broad	yes	body of tongue, vastus lateralis, quadriceps femoris
CEP63	282	ubiquitous	marker	calcaneal tendon, colonic epithelium, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CEP63	1,437
KY	902

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CEP63	Q96MT8	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KY	Q8NBH2	80.04

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. Enrichment computed across 2 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
Centrosome maturation	1	253.8×	0.013	CEP63
Loss of Nlp from mitotic centrosomes	1	158.6×	0.013	CEP63
Loss of proteins required for interphase microtubule organization from the centrosome	1	158.6×	0.013	CEP63
AURKA Activation by TPX2	1	152.3×	0.013	CEP63
Recruitment of mitotic centrosome proteins and complexes	1	135.9×	0.013	CEP63
Regulation of PLK1 Activity at G2/M Transition	1	126.9×	0.013	CEP63
Mitotic G2-G2/M phases	1	126.9×	0.013	CEP63
G2/M Transition	1	126.9×	0.013	CEP63
Recruitment of NuMA to mitotic centrosomes	1	116.5×	0.013	CEP63
Anchoring of the basal body to the plasma membrane	1	113.1×	0.013	CEP63
Cilium Assembly	1	108.8×	0.013	CEP63
Mitotic Prometaphase	1	69.2×	0.017	CEP63
Organelle biogenesis and maintenance	1	66.0×	0.017	CEP63
M Phase	1	66.0×	0.017	CEP63
Cell Cycle, Mitotic	1	48.2×	0.022	CEP63
Cell Cycle	1	36.0×	0.028	CEP63

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
negative regulation of protein K63-linked ubiquitination	1	2106.5×	0.004	CEP63
de novo centriole assembly involved in multi-ciliated epithelial cell differentiation	1	1685.2×	0.004	CEP63
signal transduction in response to DNA damage	1	401.2×	0.008	CEP63
centriole replication	1	366.4×	0.008	CEP63
neuromuscular junction development	1	263.3×	0.008	KY
negative regulation of innate immune response	1	255.3×	0.008	CEP63
spindle assembly	1	221.7×	0.008	CEP63
DNA damage checkpoint signaling	1	195.9×	0.008	CEP63
muscle organ development	1	83.4×	0.016	KY
protein stabilization	1	33.4×	0.036	CEP63
cell division	1	23.1×	0.047	CEP63
proteolysis	1	17.1×	0.058	KY

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
KY	0	0
CEP63	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	1	KY
E	Difficult family or no structure, no drug	1	CEP63

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)
KY	0	—
CEP63	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.