Microcephaly 20, primary, autosomal recessive

Summary

Microcephaly 20, primary, autosomal recessive (MONDO:0054761) is a disease caused by KIF14 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: KIF14 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 45

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microcephaly 20, primary, autosomal recessive
Mondo ID	MONDO:0054761
OMIM	617914
DOID	DOID:0051031
UMLS	C4693572
MedGen	1641618
GARD	0016268
Is cancer (heuristic)	no

Also known as: MCPH20

Data availability: 45 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › autosomal recessive primary microcephaly › microcephaly 20, primary, autosomal recessive

Related subtypes (28): microcephaly 1, primary, autosomal recessive, microcephaly with simplified gyral pattern, microcephaly 2, primary, autosomal recessive, with or without cortical malformations, microcephaly 4, primary, autosomal recessive, microcephaly 3, primary, autosomal recessive, microcephaly 5, primary, autosomal recessive, microcephaly 7, primary, autosomal recessive, microcephaly 8, primary, autosomal recessive, microcephaly 9, primary, autosomal recessive, microcephalic primordial dwarfism due to ZNF335 deficiency, microcephaly 11, primary, autosomal recessive, microcephaly 13, primary, autosomal recessive, microcephaly 12, primary, autosomal recessive, microcephaly 14, primary, autosomal recessive, microcephaly 15, primary, autosomal recessive, microcephaly 16, primary, autosomal recessive, microcephaly 17, primary, autosomal recessive, microcephaly 28, primary, autosomal recessive, microcephaly 29, primary, autosomal recessive, microcephaly 24, primary, autosomal recessive, microcephaly 25, primary, autosomal recessive, microcephaly 19, primary, autosomal recessive, microcephaly 21, primary, autosomal recessive, microcephaly 22, primary, autosomal recessive, microcephaly 23, primary, autosomal recessive, microcephaly with or without short stature, microcephaly 30, primary, autosomal recessive, microcephaly 31, primary, autosomal recessive

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

45 retrieved; paginated sample, class counts are floors:

14 uncertain significance, 14 likely pathogenic, 7 pathogenic, 4 conflicting classifications of pathogenicity, 3 benign, 1 pathogenic/likely pathogenic, 1 likely benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1678037	NM_014875.3(KIF14):c.103C>T (p.Arg35Ter)	KIF14	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2573572	NM_014875.3(KIF14):c.2354_2355del (p.Lys785fs)	KIF14	Pathogenic	criteria provided, single submitter
3902527	NM_014875.3(KIF14):c.3910C>T (p.Gln1304Ter)	KIF14	Pathogenic	criteria provided, single submitter
503565	NM_014875.3(KIF14):c.263T>A (p.Leu88Ter)	KIF14	Pathogenic	no assertion criteria provided
503566	NM_014875.3(KIF14):c.2480_2482del (p.Val827del)	KIF14	Pathogenic	no assertion criteria provided
503568	NM_014875.3(KIF14):c.2545C>G (p.His849Asp)	KIF14	Pathogenic	no assertion criteria provided
503570	NM_014875.3(KIF14):c.246del (p.Asn83fs)	KIF14	Pathogenic	no assertion criteria provided
503571	NM_014875.3(KIF14):c.4432del (p.Ser1478fs)	KIF14	Pathogenic	no assertion criteria provided
2664235	NM_014875.3(KIF14):c.2813+2dup	KIF14	Likely pathogenic	criteria provided, single submitter
3242257	NM_014875.3(KIF14):c.4475del (p.Asp1492fs)	KIF14	Likely pathogenic	criteria provided, single submitter
3576534	NM_014875.3(KIF14):c.4428+1G>T	KIF14	Likely pathogenic	criteria provided, single submitter
3576537	NM_014875.3(KIF14):c.4094del (p.Ser1364_Ser1365insTer)	KIF14	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3576539	NM_014875.3(KIF14):c.4069C>T (p.Gln1357Ter)	KIF14	Likely pathogenic	criteria provided, single submitter
3576543	NM_014875.3(KIF14):c.3887-8_3930delinsAAA	KIF14	Likely pathogenic	criteria provided, single submitter
3576547	NM_014875.3(KIF14):c.3640_3641del (p.Leu1214fs)	KIF14	Likely pathogenic	criteria provided, single submitter
3576554	NM_014875.3(KIF14):c.3619C>T (p.Gln1207Ter)	KIF14	Likely pathogenic	criteria provided, single submitter
3576558	NM_014875.3(KIF14):c.1989_1993del (p.Glu664fs)	KIF14	Likely pathogenic	criteria provided, single submitter
3576560	NM_014875.3(KIF14):c.1123G>T (p.Glu375Ter)	KIF14	Likely pathogenic	criteria provided, single submitter
3576563	NM_014875.3(KIF14):c.1021_1022del (p.Val341fs)	KIF14	Likely pathogenic	criteria provided, single submitter
3576566	NM_014875.3(KIF14):c.955del (p.Ser319fs)	KIF14	Likely pathogenic	criteria provided, single submitter
503567	NM_014875.3(KIF14):c.4071G>A (p.Gln1357=)	KIF14	Likely pathogenic	criteria provided, single submitter
503569	NM_014875.3(KIF14):c.3662G>T (p.Gly1221Val)	KIF14	Likely pathogenic	criteria provided, single submitter
288199	NM_014875.3(KIF14):c.346G>A (p.Glu116Lys)	KIF14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
715554	NM_014875.3(KIF14):c.1184C>T (p.Thr395Met)	KIF14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
740813	NM_014875.3(KIF14):c.4843G>A (p.Gly1615Ser)	KIF14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
978236	NM_014875.3(KIF14):c.14G>T (p.Ser5Ile)	KIF14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1030439	NM_014875.3(KIF14):c.1570C>G (p.His524Asp)	KIF14	Uncertain significance	criteria provided, single submitter
1033305	NM_014875.3(KIF14):c.1147A>G (p.Met383Val)	KIF14	Uncertain significance	criteria provided, multiple submitters, no conflicts
1033306	NM_014875.3(KIF14):c.1813G>T (p.Ala605Ser)	KIF14	Uncertain significance	criteria provided, multiple submitters, no conflicts
1033714	NM_014875.3(KIF14):c.4247C>A (p.Ala1416Asp)	KIF14	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
KIF14	Definitive	Autosomal recessive	autosomal recessive primary microcephaly	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KIF14	Orphanet:2512	Autosomal recessive primary microcephaly
KIF14	Orphanet:439897	Lethal fetal cerebrorenogenitourinary agenesis/hypoplasia 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
KIF14	HGNC:19181	ENSG00000118193	Q15058	Kinesin-like protein KIF14	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KIF14	Kinesin-like protein KIF14	Microtubule motor protein that binds to microtubules with high affinity through each tubulin heterodimer and has an ATPase activity.

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)
KIF14	Other/Unknown	no		FHA_dom, Kinesin_motor_dom, SMAD_FHA_dom_sf

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
endometrium epithelium	1
secondary oocyte	1
trabecular bone tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KIF14	144	ubiquitous	marker	secondary oocyte, endometrium epithelium, trabecular bone tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KIF14	6,868

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KIF14	Q15058	65.68

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
RHO GTPases activate CIT	1	601.0×	0.010	KIF14
RND1 GTPase cycle	1	265.6×	0.010	KIF14
RND2 GTPase cycle	1	259.6×	0.010	KIF14
RHO GTPase Effectors	1	68.0×	0.027	KIF14
RHO GTPase cycle	1	60.1×	0.027	KIF14
Signaling by Rho GTPases	1	34.2×	0.034	KIF14
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.034	KIF14
Signal Transduction	1	10.2×	0.098	KIF14

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
cerebellar granular layer structural organization	1	16852.0×	9e-04	KIF14
regulation of cell maturation	1	16852.0×	9e-04	KIF14
cerebellar Purkinje cell layer structural organization	1	8426.0×	0.001	KIF14
negative regulation of integrin activation	1	5617.3×	0.001	KIF14
regulation of Rap protein signal transduction	1	4213.0×	0.001	KIF14
cerebellar cortex development	1	2106.5×	0.002	KIF14
activation of protein kinase activity	1	1532.0×	0.002	KIF14
regulation of G2/M transition of mitotic cell cycle	1	1296.3×	0.002	KIF14
cell proliferation in forebrain	1	1296.3×	0.002	KIF14
regulation of myelination	1	887.0×	0.003	KIF14
olfactory bulb development	1	766.0×	0.003	KIF14
regulation of neuron apoptotic process	1	702.2×	0.003	KIF14
establishment of protein localization	1	432.1×	0.005	KIF14
positive regulation of cytokinesis	1	401.2×	0.005	KIF14
mitotic metaphase chromosome alignment	1	383.0×	0.005	KIF14
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	1	374.5×	0.005	KIF14
substrate adhesion-dependent cell spreading	1	343.9×	0.005	KIF14
regulation of cell adhesion	1	306.4×	0.005	KIF14
regulation of G1/S transition of mitotic cell cycle	1	306.4×	0.005	KIF14
microtubule-based movement	1	295.6×	0.005	KIF14
hippocampus development	1	230.8×	0.006	KIF14
regulation of cell growth	1	221.7×	0.006	KIF14
cerebral cortex development	1	205.5×	0.006	KIF14
regulation of cell migration	1	157.5×	0.008	KIF14
negative regulation of neuron apoptotic process	1	110.9×	0.010	KIF14
proteasome-mediated ubiquitin-dependent protein catabolic process	1	52.2×	0.021	KIF14
cell division	1	46.2×	0.023	KIF14
negative regulation of apoptotic process	1	34.8×	0.030	KIF14
positive regulation of cell population proliferation	1	33.6×	0.030	KIF14

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
KIF14	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
KIF14	1	Binding:1

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	KIF14

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)
KIF14	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.