NOTUM

protein-coding

notum, palmitoleoyl-protein carboxylesterase

Gene summary

Enables palmitoleyl hydrolase activity. Involved in negative regulation of Wnt signaling pathway and protein depalmitoleylation. Acts upstream of or within bone development and regulation of bone mineralization. Predicted to be located in endoplasmic reticulum lumen and extracellular region. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_178493.6

Inheritance

—

ClinVar variants

U:82B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.34

Max pathogenic AF

—

Genomic locus

chr17:81,952,507-81,961,840

External References & Databases

Ensembl (ENSG00000185269)

Transcript & Mutation Effects

hg38 • Region Span ~9.3 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 NOTUM variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 82

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_178493.6. 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				3 clinvar		3
missense			81 clinvar	2 clinvar	1 clinvar	84
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	82	5	1	88

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_178493.6	RefSeq	NP_848588.3	11	MANE Select
ENST00000409678.8	Ensembl	ENSP00000387310.3	11	MANE Select
ENST00000425009.1	Ensembl	ENSP00000407905.1	7	Standard
ENST00000477214.5	Ensembl	ENSP00000464734.1	7	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
notum1a	Danio rerio	Structure: post-vent region Quality: curved abnormal

Gene / Model

Organism

Observed Phenotype

notum1a

Danio rerio

Structure: post-vent region

Quality: curved

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Wnt signaling pathway - Homo sapiens (human)
Wnt Signaling Pathway
Signal Transduction
Post-translational protein phosphorylation
Post-translational protein modification

Biological Process

Wnt signaling pathway
negative regulation of Wnt signaling pathway
post-translational protein modification
cellular protein metabolic process
negative regulation of canonical Wnt signaling pathway

Molecular Function

phospholipase C activity
palmitoleyl hydrolase activity

Cellular Component

extracellular region
endoplasmic reticulum lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000409678
Coding exons: 11
Length: 9329
Individuals with no LoFs: 125707
Homozygous LoFs: 0
Heterozygous LoFs: 37
Defined: 125744
p: 0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.44	235	306	0.768	0.0000187	3186
Missense (PolyPhen)		71	115.93	0.61244		1260
Synonymous	-0.904	153	139	1.10	0.00000965	998
Loss of Function	3.30	10	29.2	0.342	0.00000169	273

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000055	0.000054	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00016	0.00016	rare
South Asian	0.00030	0.00026	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Carboxylesterase that acts as a key negative regulator of the Wnt signaling pathway by specifically mediating depalmitoleoylation of WNT proteins. Serine palmitoleoylation of WNT proteins is required for efficient binding to frizzled receptors (PubMed:25731175). {ECO:0000269|PubMed:25731175}.;

Recessive Scores

pRec: 0.124

Intolerance Scores

LoFtool: 0.197
RVIS EVS: -0.47
RVIS percentile EVS: 23.43

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.584

Gene Damage Prediction

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