Cardiomyopathy, familial restrictive, 6

Summary

Cardiomyopathy, familial restrictive, 6 (MONDO:0030330) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cardiomyopathy, familial restrictive, 6
Mondo ID	MONDO:0030330
OMIM	619433
DOID	DOID:0061025
UMLS	C5543638
MedGen	1780781
GARD	0025540
Is cancer (heuristic)	no

Also known as: cardiomyopathy, familial restrictive, 6 · RCM6

Data availability: 6 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › cardiomyopathy › intrinsic cardiomyopathy › restrictive cardiomyopathy › familial restrictive cardiomyopathy › cardiomyopathy, familial restrictive, 6

Related subtypes (9): cardiomyopathy, familial restrictive, 1, Gaucher disease type I, glycogen storage disease II, idiopathic hypereosinophilic syndrome, cardiomyopathy, familial restrictive, 2, cardiomyopathy, familial restrictive, 3, dilated cardiomyopathy 1KK, atrial standstill, ATTRV122I amyloidosis

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

6 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 1 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1179003	NM_005733.3(KIF20A):c.1909del (p.Tyr637fs)	KIF20A	Pathogenic	no assertion criteria provided
3367014	NM_005733.3(KIF20A):c.1423C>T (p.Arg475Ter)	KIF20A	Likely pathogenic	criteria provided, single submitter
1179002	NM_005733.3(KIF20A):c.544C>T (p.Arg182Trp)	KIF20A	Uncertain significance	criteria provided, single submitter
3367019	NM_005733.3(KIF20A):c.2416A>G (p.Lys806Glu)	KIF20A	Uncertain significance	criteria provided, single submitter
1232300	NM_005681.4(TAF1A):c.1021G>A (p.Gly341Arg)	TAF1A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1706560	NM_005681.4(TAF1A):c.781A>C (p.Thr261Pro)	TAF1A	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
KIF20A	Supportive	Autosomal dominant	familial isolated restrictive cardiomyopathy	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KIF20A	Orphanet:75249	Familial isolated restrictive cardiomyopathy
TAF1A	Orphanet:154	Familial isolated dilated cardiomyopathy

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
KIF20A	HGNC:9787	ENSG00000112984	O95235	Kinesin-like protein KIF20A	gencc,clinvar
TAF1A	HGNC:11532	ENSG00000143498	Q15573	TATA box-binding protein-associated factor RNA polymerase I subunit A	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KIF20A	Kinesin-like protein KIF20A	Mitotic kinesin required for chromosome passenger complex (CPC)-mediated cytokinesis.
TAF1A	TATA box-binding protein-associated factor RNA polymerase I subunit A	Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (pre-initiation complex) during RNA polymerase I-dependent transcription.

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
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KIF20A	Enzyme (other)	yes	5.6.1.3	Kinesin_motor_dom, Kinesin_motor_CS, P-loop_NTPase
TAF1A	Other/Unknown	no		RNA_pol_I_TAF1A/TAFI48_chr, TAF1A, SL1/TIF-IB_Component

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
oocyte	2
primordial germ cell in gonad	1
ventricular zone	1
male germ line stem cell (sensu Vertebrata) in testis	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KIF20A	183	ubiquitous	marker	ventricular zone, primordial germ cell in gonad, oocyte
TAF1A	220	ubiquitous	yes	oocyte, secondary oocyte, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KIF20A	5,046
TAF1A	1,380

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KIF20A	O95235	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TAF1A	Q15573	86.29

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 27. 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
Mitotic Telophase/Cytokinesis	1	713.8×	0.034	KIF20A
Positive epigenetic regulation of rRNA expression	1	173.0×	0.034	TAF1A
RNA Polymerase I Transcription Termination	1	163.1×	0.034	TAF1A
RNA Polymerase I Promoter Clearance	1	146.4×	0.034	TAF1A
RNA Polymerase I Transcription	1	142.8×	0.034	TAF1A
Negative epigenetic regulation of rRNA expression	1	129.8×	0.034	TAF1A
RNA Polymerase I Transcription Initiation	1	112.0×	0.034	TAF1A
Kinesins	1	89.2×	0.034	KIF20A
SIRT1 negatively regulates rRNA expression	1	85.2×	0.034	TAF1A
Golgi-to-ER retrograde transport	1	66.4×	0.034	KIF20A
B-WICH complex positively regulates rRNA expression	1	60.7×	0.034	TAF1A
RNA Polymerase I Promoter Escape	1	60.7×	0.034	TAF1A
COPI-dependent Golgi-to-ER retrograde traffic	1	55.4×	0.034	KIF20A
NoRC negatively regulates rRNA expression	1	52.4×	0.034	TAF1A
Intra-Golgi and retrograde Golgi-to-ER traffic	1	52.4×	0.034	KIF20A
MHC class II antigen presentation	1	44.6×	0.038	KIF20A
Epigenetic regulation of gene expression	1	35.7×	0.043	TAF1A
Factors involved in megakaryocyte development and platelet production	1	33.2×	0.043	KIF20A
M Phase	1	33.0×	0.043	KIF20A
Cell Cycle, Mitotic	1	24.1×	0.055	KIF20A
Membrane Trafficking	1	18.5×	0.064	KIF20A
Hemostasis	1	18.0×	0.064	KIF20A
Cell Cycle	1	18.0×	0.064	KIF20A
Vesicle-mediated transport	1	17.4×	0.064	KIF20A
Adaptive Immune System	1	14.9×	0.071	KIF20A
Gene expression (Transcription)	1	8.9×	0.113	TAF1A
Immune System	1	6.5×	0.148	KIF20A

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
transcription by RNA polymerase I	1	702.2×	0.009	TAF1A
midbody abscission	1	366.4×	0.009	KIF20A
microtubule bundle formation	1	255.3×	0.009	KIF20A
regulation of cytokinesis	1	210.7×	0.009	KIF20A
microtubule-based movement	1	147.8×	0.010	KIF20A
mitotic cytokinesis	1	129.6×	0.010	KIF20A
transcription by RNA polymerase II	1	35.3×	0.032	TAF1A
protein transport	1	21.9×	0.045	KIF20A

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 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
KIF20A	0	0
TAF1A	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
KIF20A	10	Binding:10
TAF1A	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KIF20A	5.6.1.3	plus-end-directed kinesin ATPase

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	KIF20A
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	TAF1A

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)
KIF20A	10	—
TAF1A	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.