Microcephaly 15, primary, autosomal recessive

Summary

Microcephaly 15, primary, autosomal recessive (MONDO:0014660) is a disease caused by MFSD2A (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: MFSD2A (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 16

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microcephaly 15, primary, autosomal recessive
Mondo ID	MONDO:0014660
OMIM	616486
DOID	DOID:0070277
UMLS	C4225310
MedGen	895496
GARD	0016123
Is cancer (heuristic)	no

Also known as: MCPH15 · microcephaly 15, primary, autosomal recessive · neurodevelopmental disorder with progressive microcephaly, spasticity, and brain abnormalities

Data availability: 16 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 15, 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 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

16 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 5 pathogenic, 2 conflicting classifications of pathogenicity, 1 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1700576	NM_032793.5(MFSD2A):c.1386_1435del (p.Gln462fs)	MFSD2A	Pathogenic	no assertion criteria provided
1700577	NM_032793.5(MFSD2A):c.750_753del (p.Cys251fs)	MFSD2A	Pathogenic	no assertion criteria provided
1700578	NM_032793.5(MFSD2A):c.556+1G>A	MFSD2A	Pathogenic	no assertion criteria provided
372260	NM_032793.5(MFSD2A):c.476C>T (p.Thr159Met)	MFSD2A	Pathogenic	criteria provided, single submitter
372262	NM_032793.5(MFSD2A):c.1016C>T (p.Ser339Leu)	MFSD2A	Pathogenic	no assertion criteria provided
522579	NM_032793.5(MFSD2A):c.1205C>A (p.Pro402His)	MFSD2A	Pathogenic/Likely pathogenic	no assertion criteria provided
1806235	NM_032793.5(MFSD2A):c.228+8G>A	MFSD2A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
372261	NM_032793.5(MFSD2A):c.497C>T (p.Ser166Leu)	MFSD2A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029145	NM_032793.5(MFSD2A):c.379G>C (p.Val127Leu)	MFSD2A	Uncertain significance	criteria provided, single submitter
1339121	NM_032793.5(MFSD2A):c.874G>A (p.Gly292Ser)	MFSD2A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1806237	NM_032793.5(MFSD2A):c.1394G>A (p.Arg465His)	MFSD2A	Uncertain significance	criteria provided, multiple submitters, no conflicts
2433741	NM_032793.5(MFSD2A):c.446T>C (p.Leu149Pro)	MFSD2A	Uncertain significance	criteria provided, single submitter
3254815	NM_032793.5(MFSD2A):c.1414A>C (p.Met472Leu)	MFSD2A	Uncertain significance	criteria provided, single submitter
417866	NM_032793.5(MFSD2A):c.661G>A (p.Val221Ile)	MFSD2A	Uncertain significance	no assertion criteria provided
4845353	NM_032793.5(MFSD2A):c.621_632del (p.Gln207_Pro211delinsHis)	MFSD2A	Uncertain significance	criteria provided, single submitter
1598360	NM_032793.5(MFSD2A):c.93+16C>A	MFSD2A	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
MFSD2A	Definitive	Autosomal recessive	microcephaly 15, primary, autosomal recessive	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MFSD2A	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
MFSD2A	HGNC:25897	ENSG00000168389	Q8NA29	Sodium-dependent lysophosphatidylcholine symporter 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MFSD2A	Sodium-dependent lysophosphatidylcholine symporter 1	Sodium-dependent lysophosphatidylcholine (LPC) symporter, which plays an essential role for blood-brain barrier formation and function.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Transporter	1	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MFSD2A	Transporter	yes		MFS_trans_sf, MFS_2

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
ileal mucosa	1
right lobe of liver	1
skin of abdomen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MFSD2A	220	ubiquitous	marker	right lobe of liver, skin of abdomen, ileal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MFSD2A	1,054

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MFSD2A	Q8NA29	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Synthesis of PC	1	407.9×	0.002	MFSD2A

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
lysophospholipid translocation	1	16852.0×	6e-04	MFSD2A
regulation of phosphatidylethanolamine metabolic process	1	16852.0×	6e-04	MFSD2A
obsolete regulation of phosphatidylserine metabolic process	1	16852.0×	6e-04	MFSD2A
regulation of phosphatidylcholine metabolic process	1	8426.0×	9e-04	MFSD2A
carbohydrate transport	1	4213.0×	0.001	MFSD2A
negative regulation of fatty acid beta-oxidation	1	4213.0×	0.001	MFSD2A
lysophospholipid transport	1	3370.4×	0.001	MFSD2A
lipid transport across blood-brain barrier	1	3370.4×	0.001	MFSD2A
photoreceptor cell morphogenesis	1	2808.7×	0.001	MFSD2A
regulation of neuron projection arborization	1	2808.7×	0.001	MFSD2A
retina morphogenesis in camera-type eye	1	1872.4×	0.001	MFSD2A
retinal pigment epithelium development	1	1685.2×	0.001	MFSD2A
transcytosis	1	1685.2×	0.001	MFSD2A
establishment of blood-brain barrier	1	1404.3×	0.002	MFSD2A
positive regulation of triglyceride biosynthetic process	1	1296.3×	0.002	MFSD2A
very-low-density lipoprotein particle assembly	1	1203.7×	0.002	MFSD2A
long-chain fatty acid transport	1	1123.5×	0.002	MFSD2A
photoreceptor cell outer segment organization	1	1053.2×	0.002	MFSD2A
regulation of dendrite development	1	991.3×	0.002	MFSD2A
phosphatidylcholine biosynthetic process	1	802.5×	0.002	MFSD2A
regulation of multicellular organism growth	1	648.1×	0.002	MFSD2A
fatty acid transport	1	624.1×	0.002	MFSD2A
motor behavior	1	561.7×	0.002	MFSD2A
maintenance of blood-brain barrier	1	481.5×	0.003	MFSD2A
cognition	1	285.6×	0.004	MFSD2A
energy homeostasis	1	271.8×	0.005	MFSD2A
hippocampus development	1	230.8×	0.005	MFSD2A
cellular response to starvation	1	193.7×	0.006	MFSD2A
positive regulation of cell growth	1	183.2×	0.006	MFSD2A
transport across blood-brain barrier	1	179.3×	0.006	MFSD2A

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
MFSD2A	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	1	MFSD2A
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
MFSD2A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.