MFSD2A

MFSD2 lysolipid transporter A, lysophospholipid, the group of Solute carrier family 59

Basic information

Region (hg38): 1:39955111-39969968

Previous symbols: [ "MFSD2" ]

Links

ENSG00000168389 ∙ NCBI:84879 ∙ OMIM:614397 ∙ HGNC:25897 ∙ Uniprot:Q8NA29 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microcephaly 15, primary, autosomal recessive (Definitive), mode of inheritance: AR
• microcephaly 15, primary, autosomal recessive (Strong), mode of inheritance: AR
• autosomal recessive primary microcephaly (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain imaging abnormalities	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	26005865; 26005868

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MFSD2A gene.

• not provided (110 variants)
• Inborn genetic diseases (13 variants)
• Microcephaly 15, primary, autosomal recessive (7 variants)
• not specified (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MFSD2A gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	33	3	37
missense			44	2	2	48
nonsense	1					1
start loss						0
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			4	5		9
non coding			2	18	8	28
Total	1	0	49	53	13

Variants in MFSD2A

This is a list of pathogenic ClinVar variants found in the MFSD2A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-39955305-G-A		Inborn genetic diseases	Uncertain significance (Sep 22, 2023)
1-39955328-G-T			Likely benign (Jul 14, 2022)
1-39955331-G-A			Likely benign (Feb 27, 2018)
1-39955332-G-T		Inborn genetic diseases	Uncertain significance (Jun 12, 2022)
1-39955344-AC-A			Uncertain significance (Apr 28, 2022)
1-39955369-G-T		Inborn genetic diseases	Uncertain significance (May 23, 2023)
1-39955370-C-A			Likely benign (Jan 12, 2024)
1-39955373-G-A			Likely benign (Apr 02, 2018)
1-39955388-G-C			Uncertain significance (Sep 01, 2022)
1-39955401-C-A		Microcephaly 15, primary, autosomal recessive	Benign/Likely benign (Jan 15, 2024)
1-39957067-T-C			Likely benign (Apr 16, 2022)
1-39957094-C-T			Uncertain significance (Oct 24, 2022)
1-39957115-T-G			Uncertain significance (Apr 26, 2021)
1-39957122-T-C			Likely benign (Jul 31, 2023)
1-39957156-C-T			Likely benign (Dec 10, 2023)
1-39957170-G-A		MFSD2A-related disorder	Likely benign (May 15, 2023)
1-39957183-G-T			Uncertain significance (Jun 21, 2023)
1-39957198-A-C			Uncertain significance (Jul 27, 2022)
1-39957200-C-T			Likely benign (Aug 01, 2018)
1-39957229-G-A		Microcephaly 15, primary, autosomal recessive	Uncertain significance (Aug 28, 2019)
1-39957240-C-T			Likely benign (Aug 14, 2023)
1-39958645-A-G			Likely benign (Jan 08, 2024)
1-39958655-C-T			Likely benign (Dec 23, 2023)
1-39958669-A-T			Uncertain significance (Aug 19, 2022)
1-39958673-AGTT-A		8 conditions	Pathogenic (-)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MFSD2A	protein_coding	protein_coding	ENST00000372809	14	14837

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0110	0.989	125714	0	33	125747	0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.04	211	312	0.676	0.0000178	3509
Missense in Polyphen		58	138.22	0.41962		1552
Synonymous	1.31	110	129	0.853	0.00000766	1120
Loss of Function	3.47	9	29.2	0.308	0.00000143	326

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00114	0.00114
Ashkenazi Jewish	0.00	0.00
East Asian	0.000116	0.000109
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.0000616	0.0000615
Middle Eastern	0.000116	0.000109
South Asian	0.0000654	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Sodium-dependent lysophosphatidylcholine (LPC) symporter, which plays an essential role for blood-brain barrier formation and function (By similarity). Specifically expressed in endothelium of the blood-brain barrier of micro-vessels and transports LPC into the brain (By similarity). Transport of LPC is essential because it constitutes the major mechanism by which docosahexaenoic acid (DHA), an omega-3 fatty acid that is essential for normal brain growth and cognitive function, enters the brain (PubMed:26005868). Transports LPC carrying long-chain fatty acids such LPC oleate and LPC palmitate with a minimum acyl chain length of 14 carbons (By similarity). Does not transport docosahexaenoic acid in unesterified fatty acid (By similarity). Specifically required for blood-brain barrier formation and function, probably by mediating lipid transport (By similarity). Not required for central nervous system vascular morphogenesis (By similarity). Acts as a transporter for tunicamycin, an inhibitor of asparagine-linked glycosylation (PubMed:21677192). In placenta, acts as a receptor for ERVFRD-1/syncytin-2 and is required for trophoblast fusion (PubMed:18988732, PubMed:23177091). {ECO:0000250|UniProtKB:Q9DA75, ECO:0000269|PubMed:18988732, ECO:0000269|PubMed:21677192, ECO:0000269|PubMed:23177091, ECO:0000269|PubMed:26005868}.
• Disease: DISEASE: Microcephaly 15, primary, autosomal recessive (MCPH15) [MIM:616486]: A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age, sex and ethnically matched mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. {ECO:0000269|PubMed:26005865, ECO:0000269|PubMed:26005868}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Metabolism of lipids;Metabolism;Synthesis of PC;Glycerophospholipid biosynthesis;Phospholipid metabolism (Consensus)

Recessive Scores

• pRec: 0.0954

Intolerance Scores

• loftool: 0.131
• rvis_EVS: -0.49
• rvis_percentile_EVS: 22.36

Haploinsufficiency Scores

• pHI: 0.0802
• hipred: Y
• hipred_score: 0.688
• ghis: 0.531

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.231

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Mfsd2a
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); growth/size/body region phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; pigmentation phenotype

Zebrafish Information Network

• Gene name: mfsd2aa
• Affected structure: cranial vasculature
• Phenotype tag: abnormal
• Phenotype quality: porous

Gene ontology

• Biological process: phosphatidylcholine biosynthetic process;carbohydrate transport;fatty acid transport;hippocampus development;transcytosis;lysophospholipid transport;transmembrane transport;establishment of blood-brain barrier;organic substance transport;lipid transport across blood-brain barrier
• Cellular component: endoplasmic reticulum membrane;plasma membrane;integral component of plasma membrane
• Molecular function: transporter activity;phospholipid transporter activity;fatty acid transmembrane transporter activity;symporter activity;lysophospholipid transporter activity