MDGA1

protein-coding

MAM domain containing glycosylphosphatidylinositol anchor 1, the group of I-set domain containing

Gene summary

This gene encodes a glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein that is expressed predominantly in the developing nervous system. In addition to possessing several cell adhesion molecule-like domains, the mature protein has six Ig-like domains, a single fibronectin type III domain, a MAM domain and a C-terminal GPI-anchoring site. Studies in other mammals suggest this protein plays a role in cell adhesion, migration, and axon guidance and, in the developing brain, neuronal migration. In humans, this gene is associated with bipolar disorder and schizophrenia. [provided by RefSeq, Oct 2016]

MANE transcript

NM_153487.4

Inheritance

—

ClinVar variants

U:139B:9

Top phenotype

Mediastinal germ cell tumor

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chr6:37,630,679-37,699,306

External References & Databases

Ensembl (ENSG00000112139)

Transcript & Mutation Effects

hg38 • Region Span ~68.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MDGA1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 130

not providedTotal: 11

Mediastinal germ cell tumorTotal: 1

Acute megakaryoblastic leukemiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_153487.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar	3 clinvar	5
missense			133 clinvar	3 clinvar	1 clinvar	137
nonsense						0
start loss						0
frameshift			4 clinvar			4
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	139	5	4	148

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_153487.4	RefSeq	NP_705691.1	17	MANE Select
ENST00000434837.8	Ensembl	ENSP00000402584.2	17	MANE Select
ENST00000418178.2	Ensembl	ENSP00000393330.2	4	Standard
ENST00000502298.1	Ensembl	ENSP00000425911.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational modification: synthesis of GPI-anchored proteins
Post-translational protein modification
Metabolism of proteins

Biological Process

neuron migration
brain development
spinal cord association neuron differentiation
regulation of synaptic membrane adhesion
regulation of presynapse assembly

Molecular Function

molecular_function

Cellular Component

extracellular region
extracellular space
plasma membrane
anchored component of plasma membrane
GABA-ergic synapse

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000434837
Coding exons: 17
Length: 66799
Individuals with no LoFs: 124651
Homozygous LoFs: 0
Heterozygous LoFs: 18
Defined: 124669
p: 0.0000722

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.57	404	578	0.699	0.0000365	6078
Missense (PolyPhen)		182	286.05	0.63624		3036
Synonymous	0.418	239	247	0.966	0.0000161	1979
Loss of Function	5.03	7	42.3	0.166	0.00000227	457

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for radial migration of cortical neurons in the superficial layer of the neocortex (By similarity). Plays a role in the formation or maintenance of inhibitory synapses. May function by inhibiting the activity of NLGN2. {ECO:0000250, ECO:0000269|PubMed:23248271}.;

Intolerance Scores

RVIS EVS: -1.13
RVIS percentile EVS: 6.56

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.463

Gene Damage Prediction

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