GALNT12

protein-coding

polypeptide N-acetylgalactosaminyltransferase 12, the group of Polypeptide N-acetylgalactosaminyltransferases

Gene summary

This gene encodes a member of a family of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases, which catalyze the transfer of N-acetylgalactosamine (GalNAc) from UDP-GalNAc to a serine or threonine residue on a polypeptide acceptor in the initial step of O-linked protein glycosylation. Mutations in this gene are associated with an increased susceptibility to colorectal cancer.[provided by RefSeq, Mar 2011]

MANE transcript

NM_024642.5

Inheritance

ClinVar variants

P:2U:1155B:549

Top phenotype

Colorectal cancer, susceptibility to, 1

gnomAD constraint

pLI —, LoF o/e 0.59

Max pathogenic AF

—

Genomic locus

chr9:98,807,670-98,850,081

External References & Databases

Ensembl (ENSG00000119514)

Transcript & Mutation Effects

hg38 • Region Span ~42.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

colorectal cancer, susceptibility to, 1LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0012132

Submitter: ClinGen

colorectal cancer, susceptibility to, 1LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0012132

Submitter: Labcorp Genetics (formerly Invitae)

colorectal cancer, susceptibility to, 1LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0012132

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Colorectal cancer, susceptibility to, 1AD

Manifestation: Oncologic

Intervention: Oncologic

Rationale: Surveillance for colorectal neoplasms may allow early diagnosis and treatment of tumors, which may reduce morbidity and mortality

Refs: 19617566; 22461326

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GALNT12 variants in ClinVar

9 Conditions Cataloged

not specifiedTotal: 1532

not providedTotal: 708

Colorectal cancer, susceptibility to, 1Total: 607

GALNT12-related disorderTotal: 41

Hereditary cancer-predisposing syndromeTotal: 12

Familial colorectal cancerTotal: 1

Adenomatous polyposis coli, attenuatedTotal: 1

Breast neoplasmTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024642.5. 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			4 clinvar	418 clinvar	61 clinvar	483
missense			1045 clinvar	69 clinvar	1 clinvar	1115
nonsense		1 clinvar	34 clinvar			35
start loss			7 clinvar			7
frameshift		1 clinvar	46 clinvar			47
splice donor/acceptor (+/-2bp)			19 clinvar			19
Total	0	2	1155	487	62	1706

Highest pathogenic variant AF is 0.0000059265462

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024642.5	RefSeq	NP_078918.3	10	MANE Select
ENST00000375011.4	Ensembl	ENSP00000364150.3	10	MANE Select
ENST00000610463.1	Ensembl	ENSP00000477657.1	2	Standard
ENST00000931577.1	Ensembl	ENSP00000601636.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Mucin type O-glycan biosynthesis - Homo sapiens (human)
Post-translational protein modification
Metabolism of proteins
mucin core 1 and core 2 <i>O</i>-glycosylation
O-Glycan biosynthesis

Biological Process

O-glycan processing

Molecular Function

polypeptide N-acetylgalactosaminyltransferase activity
carbohydrate binding
metal ion binding

Cellular Component

Golgi membrane
Golgi apparatus
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000375011
Coding exons: 10
Length: 42383
Individuals with no LoFs: 125714
Homozygous LoFs: 0
Heterozygous LoFs: 34
Defined: 125748
p: 0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.131	272	278	0.978	0.0000172	3735
Missense (PolyPhen)		151	150.64	1.0024		1775
Synonymous	0.143	112	114	0.983	0.00000757	1156
Loss of Function	1.77	13	22.0	0.592	9.66e-7	284

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00043	0.00043	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00027	0.00027	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00012	0.00012	rare
South Asian	0.00013	0.00013	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D- galactosamine residue to a serine or threonine residue on the protein receptor. Has activity toward non-glycosylated peptides such as Muc5AC, Muc1a and EA2, and no detectable activity with Muc2 and Muc7. Displays enzymatic activity toward the Gal-NAc- Muc5AC glycopeptide, but no detectable activity to mono-GalNAc- glycosylated Muc1a, Muc2, Muc7 and EA2. May play an important role in the initial step of mucin-type oligosaccharide biosynthesis in digestive organs.;
Disease: DISEASE: Colorectal cancer 1 (CRCS1) [MIM:608812]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. {ECO:0000269|PubMed:19617566, ECO:0000269|PubMed:22461326, ECO:0000269|PubMed:24115450}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. The role of GALNT12 in colon cancer susceptibility is however subject to discussion: studies on 103 probants with colorectal cancer 1 (CRCS1) suggest that it does not act as a major contributor of CRCS1 (PubMed:24115450). {ECO:0000269|PubMed:24115450}.;

Recessive Scores

pRec: 0.104

Intolerance Scores

LoFtool: 0.672
RVIS EVS: -0.73
RVIS percentile EVS: 14.08

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.780

Gene Damage Prediction

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