Microcephaly 14, primary, autosomal recessive

Summary

Microcephaly 14, primary, autosomal recessive (MONDO:0014623) is a disease caused by SASS6 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SASS6 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microcephaly 14, primary, autosomal recessive
Mondo ID	MONDO:0014623
OMIM	616402
DOID	DOID:0070279
UMLS	C4225338
MedGen	906798
GARD	0016105
Is cancer (heuristic)	no

Also known as: autosomal recessive primary microcephaly caused by mutation in SASS6 · MCPH14 · microcephaly 14, primary, autosomal recessive · SASS6 autosomal recessive primary microcephaly

Data availability: 14 ClinVar variants · 4 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 14, 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 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 20, 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

14 retrieved; paginated sample, class counts are floors:

3 benign, 3 likely pathogenic, 2 pathogenic, 2 benign/likely benign, 1 uncertain significance, 1 conflicting classifications of pathogenicity, 1 likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
192231	NM_194292.3(SASS6):c.185T>C (p.Ile62Thr)	SASS6	Pathogenic	no assertion criteria provided
977771	NM_194292.3(SASS6):c.127-13A>G	SASS6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
977772	NM_194292.3(SASS6):c.1867+2T>A	SASS6	Pathogenic	no assertion criteria provided
2502836	NM_194292.3(SASS6):c.170del (p.Leu57fs)	SASS6	Likely pathogenic	criteria provided, single submitter
2506119	NM_194292.3(SASS6):c.497C>A (p.Ser166Ter)	SASS6	Likely pathogenic	criteria provided, single submitter
977344	NM_194292.3(SASS6):c.170dup (p.Leu57fs)	SASS6	Likely pathogenic	criteria provided, single submitter
1802193	NM_194292.3(SASS6):c.1057-6_1057-2del	SASS6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1679253	NM_194292.3(SASS6):c.134T>A (p.Val45Asp)	SASS6	Uncertain significance	criteria provided, multiple submitters, no conflicts
1263477	NM_194292.3(SASS6):c.776C>T (p.Ala259Val)	SASS6	Benign	criteria provided, multiple submitters, no conflicts
436635	NM_194292.3(SASS6):c.86G>A (p.Ser29Asn)	SASS6	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
720071	NM_194292.3(SASS6):c.873G>C (p.Arg291=)	SASS6	Likely benign	criteria provided, multiple submitters, no conflicts
734406	NM_194292.3(SASS6):c.1835G>A (p.Arg612His)	SASS6	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
738128	NM_194292.3(SASS6):c.312-4A>C	SASS6	Benign	criteria provided, multiple submitters, no conflicts
781776	NM_194292.3(SASS6):c.735A>G (p.Gln245=)	SASS6	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
SASS6	Strong	Autosomal recessive	microcephaly 14, primary, autosomal recessive	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SASS6	Orphanet:2512	Autosomal recessive primary microcephaly

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
SASS6	HGNC:25403	ENSG00000156876	Q6UVJ0	Spindle assembly abnormal protein 6 homolog	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SASS6	Spindle assembly abnormal protein 6 homolog	Central scaffolding component of the centrioles ensuring their 9-fold symmetry.

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)
SASS6	Other/Unknown	no		SAS-6_N, SAS-6_N_sf, SAS6_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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SASS6	178	ubiquitous	marker	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
SASS6	2,336

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SASS6	Q6UVJ0	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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 centriole replication	1	3370.4×	0.002	SASS6
positive regulation of spindle assembly	1	2106.5×	0.002	SASS6
centrosome duplication	1	936.2×	0.002	SASS6
regulation of mitotic spindle organization	1	842.6×	0.002	SASS6
centriole replication	1	732.7×	0.002	SASS6
positive regulation of G1/S transition of mitotic cell cycle	1	401.2×	0.003	SASS6
spermatogenesis	1	35.2×	0.028	SASS6

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
SASS6	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	SASS6

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)
SASS6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.