CMAS

protein-coding

cytidine monophosphate N-acetylneuraminic acid synthetase

Gene summary

This gene encodes an enzyme that converts N-acetylneuraminic acid (NeuNAc) to cytidine 5'-monophosphate N-acetylneuraminic acid (CMP-NeuNAc). This process is important in the formation of sialylated glycoprotein and glycolipids. This modification plays a role in cell-cell communications and immune responses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

MANE transcript

NM_018686.6

Inheritance

ClinVar variants

U:41B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr12:22,046,218-22,065,674

External References & Databases

Ensembl (ENSG00000111726)

Transcript & Mutation Effects

hg38 • Region Span ~19.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual disabilityLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0001071

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CMAS variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 34

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018686.6. 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			1 clinvar	2 clinvar	1 clinvar	4
missense			37 clinvar	1 clinvar		38
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	41	3	1	45

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 34 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018686.6	RefSeq	NP_061156.1	8	MANE Select
ENST00000229329.7	Ensembl	ENSP00000229329.2	8	MANE Select
ENST00000534981.5	Ensembl	ENSP00000446239.1	6	Standard
ENST00000535610.5	Ensembl	ENSP00000439404.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Amino sugar and nucleotide sugar metabolism - Homo sapiens (human)
Sialuria or French Type Sialuria
Sialuria or French Type Sialuria
Amino Sugar Metabolism
G(M2)-Gangliosidosis: Variant B, Tay-sachs disease

Biological Process

N-acetylneuraminate metabolic process

Molecular Function

N-acylneuraminate cytidylyltransferase activity

Cellular Component

nucleus
nucleoplasm
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000229329
Coding exons: 8
Length: 19501
Individuals with no LoFs: 125724
Homozygous LoFs: 0
Heterozygous LoFs: 20
Defined: 125744
p: 0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.45	125	229	0.545	0.0000115	2791
Missense (PolyPhen)		25	70.472	0.35475		826
Synonymous	1.03	71	82.9	0.856	0.00000392	851
Loss of Function	3.62	5	24.3	0.206	0.00000146	269

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00017	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000056	0.000054	rare
Finnish	0.00037	0.00037	rare
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0.000067	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the activation of N-acetylneuraminic acid (NeuNAc) to cytidine 5'-monophosphate N-acetylneuraminic acid (CMP-NeuNAc), a substrate required for the addition of sialic acid. Has some activity toward NeuNAc, N-glycolylneuraminic acid (Neu5Gc) or 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (KDN).;

Recessive Scores

pRec: 0.143

Intolerance Scores

LoFtool: 0.247
RVIS EVS: -0.38
RVIS percentile EVS: 27.42

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.915

Gene Damage Prediction

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