GCM1

protein-coding

glial cells missing transcription factor 1

Gene summary

This gene encodes a DNA-binding protein with a gcm-motif (glial cell missing motif). The encoded protein is a homolog of the Drosophila glial cells missing gene (gcm). This protein binds to the GCM-motif (A/G)CCCGCAT, a novel sequence among known targets of DNA-binding proteins. The N-terminal DNA-binding domain confers the unique DNA-binding activity of this protein. [provided by RefSeq, Jul 2008]

Previous symbols:

GCMA

MANE transcript

NM_003643.4

Inheritance

—

ClinVar variants

U:50B:9

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr6:53,126,961-53,148,841

External References & Databases

Ensembl (ENSG00000137270)

Transcript & Mutation Effects

hg38 • Region Span ~21.9 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 GCM1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 52

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003643.4. 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			48 clinvar	4 clinvar		52
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	50	6	3	59

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003643.4	RefSeq	NP_003634.2	5	MANE Select
ENST00000259803.8	Ensembl	ENSP00000259803.7	5	MANE Select
ENST00001127515.1	Ensembl	ENSP00000797320.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription, DNA-templated
transcription by RNA polymerase II
anatomical structure morphogenesis
positive regulation of transcription by RNA polymerase II
astrocyte fate commitment

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription activator activity, RNA polymerase II-specific
DNA binding
DNA-binding transcription factor activity

Cellular Component

nucleus
transcription factor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000259803
Coding exons: 5
Length: 21866
Individuals with no LoFs: 125647
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 125648
p: 0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.44	181	244	0.741	0.0000138	2887
Missense (PolyPhen)		21	76.399	0.27487		851
Synonymous	0.451	88	93.5	0.941	0.00000577	808
Loss of Function	4.15	0	20.0	0.00	0.00000104	224

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcription factor involved in the control of expression of placental growth factor (PGF) and other placenta- specific genes (PubMed:10542267, PubMed:18160678). Binds to the trophoblast-specific element 2 (TSE2) of the aromatase gene enhancer (PubMed:10542267). Binds to the SYDE1 promoter (PubMed:27917469). Has a central role in mediating the differentiation of trophoblast cells along both the villous and extravillous pathways in placental development (PubMed:19219068). {ECO:0000269|PubMed:10542267, ECO:0000269|PubMed:18160678, ECO:0000269|PubMed:19219068, ECO:0000269|PubMed:27917469}.;

Recessive Scores

pRec: 0.187

Intolerance Scores

LoFtool: 0.107
RVIS EVS: -0.09
RVIS percentile EVS: 46.92

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.224

Gene Damage Prediction

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