Microcephaly 7, primary, autosomal recessive

Summary

Microcephaly 7, primary, autosomal recessive (MONDO:0012989) is a disease caused by STIL (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: STIL (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 129

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microcephaly 7, primary, autosomal recessive
Mondo ID	MONDO:0012989
MeSH	C567198
OMIM	612703
DOID	DOID:0070278
UMLS	C2675187
MedGen	436370
GARD	0015580
Is cancer (heuristic)	no

Also known as: autosomal recessive primary microcephaly caused by mutation in STIL · MCPH7 · microcephaly 7, primary, autosomal recessive · STIL autosomal recessive primary microcephaly

Data availability: 129 ClinVar variants · 3 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 7, 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 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 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

129 retrieved; paginated sample, class counts are floors:

77 uncertain significance, 19 conflicting classifications of pathogenicity, 9 benign, 6 pathogenic, 6 likely pathogenic, 5 benign/likely benign, 4 not provided, 3 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
12948	NM_001048166.1(STIL):c.3718C>T (p.Gln1240Ter)	STIL	Pathogenic	no assertion criteria provided
12949	NM_001048166.1(STIL):c.3658del (p.Leu1219_Val1220insTer)	STIL	Pathogenic	no assertion criteria provided
12950	NM_001048166.1(STIL):c.2829+1G>A	STIL	Pathogenic	no assertion criteria provided
218244	NM_001048166.1(STIL):c.453+5G>A	STIL	Pathogenic	no assertion criteria provided
4813075	NM_001048166.1(STIL):c.2960C>G (p.Ser987Ter)	STIL	Pathogenic	criteria provided, single submitter
91843	NM_001048166.1(STIL):c.2393T>G (p.Leu798Trp)	STIL	Pathogenic	no assertion criteria provided
160069	NM_001048166.1(STIL):c.895T>A (p.Phe299Ile)	STIL	Likely pathogenic	criteria provided, single submitter
1679330	NM_001048166.1(STIL):c.1078C>T (p.Gln360Ter)	STIL	Likely pathogenic	criteria provided, single submitter
1683274	NM_001048166.1(STIL):c.384dup (p.His129fs)	STIL	Likely pathogenic	criteria provided, single submitter
1705699	NM_001048166.1(STIL):c.2488_2489del (p.Asp830fs)	STIL	Likely pathogenic	criteria provided, single submitter
2433997	NM_001048166.1(STIL):c.3538_3541del (p.Asn1180fs)	STIL	Likely pathogenic	criteria provided, single submitter
977229	NM_001048166.1(STIL):c.2344_2347del (p.Leu782fs)	STIL	Likely pathogenic	no assertion criteria provided
1418596	NM_001048166.1(STIL):c.2676G>C (p.Gln892His)	STIL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
160049	NM_001048166.1(STIL):c.1136C>T (p.Ser379Phe)	STIL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
194209	NM_001048166.1(STIL):c.2362G>A (p.Val788Ile)	STIL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
194628	NM_001048166.1(STIL):c.2906A>G (p.His969Arg)	STIL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
212323	NM_001048166.1(STIL):c.3581C>T (p.Pro1194Leu)	STIL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
21357	NM_001048166.1(STIL):c.3437C>T (p.Ala1146Val)	STIL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
235445	NM_001048166.1(STIL):c.1055G>A (p.Arg352His)	STIL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
282750	NM_001048166.1(STIL):c.892A>G (p.Asn298Asp)	STIL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
297552	NM_001048166.1(STIL):c.3207T>C (p.Ala1069=)	STIL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
297558	NM_001048166.1(STIL):c.2064G>A (p.Pro688=)	STIL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
297559	NM_001048166.1(STIL):c.1699C>T (p.Pro567Ser)	STIL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
297563	NM_001048166.1(STIL):c.1005A>G (p.Glu335=)	STIL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
502127	NM_001048166.1(STIL):c.3838C>T (p.Arg1280Cys)	STIL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
546576	NM_001048166.1(STIL):c.1264C>A (p.Pro422Thr)	STIL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
737417	NM_001048166.1(STIL):c.3699C>T (p.Thr1233=)	STIL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
737418	NM_001048166.1(STIL):c.454-10G>A	STIL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
873842	NM_001048166.1(STIL):c.3579G>A (p.Thr1193=)	STIL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
874795	NM_001048166.1(STIL):c.3061C>T (p.His1021Tyr)	STIL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 7 · 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
STIL	Definitive	Autosomal recessive	autosomal recessive primary microcephaly	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
STIL	Orphanet:220386	Semilobar holoprosencephaly
STIL	Orphanet:2512	Autosomal recessive primary microcephaly
STIL	Orphanet:280195	Septopreoptic holoprosencephaly
STIL	Orphanet:93924	Lobar holoprosencephaly
STIL	Orphanet:93925	Alobar holoprosencephaly
STIL	Orphanet:93926	Midline interhemispheric variant of holoprosencephaly
STIL	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia

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
STIL	HGNC:10879	ENSG00000123473	Q15468	SCL-interrupting locus protein	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
STIL	SCL-interrupting locus protein	Immediate-early gene.

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)
STIL	Other/Unknown	no		STIL, STIL_CC, STIL_N

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
oocyte	1
primordial germ cell in gonad	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
STIL	221	ubiquitous	marker	secondary oocyte, oocyte, primordial germ cell in gonad

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
STIL	2,053

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
STIL	Q15468	5

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	STIL
embryonic axis specification	1	2407.4×	0.002	STIL
floor plate development	1	2407.4×	0.002	STIL
positive regulation of spindle assembly	1	2106.5×	0.002	STIL
notochord development	1	1685.2×	0.002	STIL
regulation of centriole replication	1	1685.2×	0.002	STIL
microtubule organizing center organization	1	1404.3×	0.002	STIL
centrosome duplication	1	936.2×	0.003	STIL
regulation of mitotic spindle organization	1	842.6×	0.003	STIL
protein localization to centrosome	1	674.1×	0.003	STIL
neural tube development	1	526.6×	0.004	STIL
positive regulation of G1/S transition of mitotic cell cycle	1	401.2×	0.004	STIL
forebrain development	1	351.1×	0.005	STIL
mitotic spindle organization	1	271.8×	0.005	STIL
heart looping	1	267.5×	0.005	STIL
determination of left/right symmetry	1	255.3×	0.005	STIL
neural tube closure	1	187.2×	0.006	STIL
smoothened signaling pathway	1	181.2×	0.006	STIL
multicellular organism growth	1	137.0×	0.008	STIL
in utero embryonic development	1	72.0×	0.015	STIL
negative regulation of apoptotic process	1	34.8×	0.029	STIL

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
STIL	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	STIL

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)
STIL	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.