NOTUM

notum, palmitoleoyl-protein carboxylesterase

Basic information

Region (hg38): 17:81952506-81961840

Links

ENSG00000185269 ∙ NCBI:147111 ∙ OMIM:609847 ∙ HGNC:27106 ∙ Uniprot:Q6P988 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NOTUM gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NOTUM gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2		2
missense			34	1	1	36
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	34	3	1

Variants in NOTUM

This is a list of pathogenic ClinVar variants found in the NOTUM region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-81953044-T-A		not specified	Uncertain significance (Dec 15, 2022)
17-81953058-T-C		not specified	Uncertain significance (Jan 22, 2024)
17-81953065-C-T		not specified	Uncertain significance (May 03, 2023)
17-81953077-G-T		not specified	Uncertain significance (Oct 29, 2021)
17-81953124-G-A		not specified	Uncertain significance (May 10, 2022)
17-81953172-G-A		not specified	Uncertain significance (Dec 15, 2022)
17-81953173-T-C			Uncertain significance (Mar 03, 2020)
17-81953226-C-A		not specified	Uncertain significance (Nov 10, 2022)
17-81953227-G-C		not specified	Uncertain significance (Apr 25, 2023)
17-81954273-A-C		not specified	Uncertain significance (Sep 28, 2022)
17-81955401-C-A		not specified	Uncertain significance (Sep 13, 2023)
17-81955412-G-A		not specified	Uncertain significance (Aug 28, 2023)
17-81955418-C-T		not specified	Uncertain significance (May 05, 2023)
17-81955425-C-T		not specified	Uncertain significance (Dec 19, 2022)
17-81955512-C-T		not specified	Uncertain significance (Mar 25, 2024)
17-81956653-G-A		not specified	Uncertain significance (Jun 29, 2023)
17-81956658-G-A		not specified	Uncertain significance (Nov 21, 2022)
17-81956724-C-T		not specified	Uncertain significance (Oct 06, 2021)
17-81956737-C-T		not specified	Uncertain significance (Sep 07, 2022)
17-81956747-G-A			Likely benign (Aug 01, 2022)
17-81956892-C-T		not specified	Uncertain significance (Oct 05, 2023)
17-81956915-G-A			Benign/Likely benign (Feb 01, 2023)
17-81956946-C-T			Benign (May 18, 2018)
17-81956996-C-G		not specified	Uncertain significance (Dec 18, 2023)
17-81958337-T-C		not specified	Uncertain significance (Nov 18, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NOTUM	protein_coding	protein_coding	ENST00000409678	11	9329

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00216	0.998	125707	0	37	125744	0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.44	235	306	0.768	0.0000187	3186
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000242	0.000239
Ashkenazi Jewish	0.0000995	0.0000992
East Asian	0.0000547	0.0000544
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000160	0.000158
Middle Eastern	0.0000547	0.0000544
South Asian	0.000300	0.000261
Other	0.00	0.00

dbNSFP

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}.
• Pathway: Wnt signaling pathway - Homo sapiens (human);Wnt Signaling Pathway;Signal Transduction;Post-translational protein phosphorylation;Post-translational protein modification;Metabolism of proteins;Release of Hh-Np from the secreting cell;Hedgehog ligand biogenesis;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);Signaling by Hedgehog (Consensus)

Recessive Scores

• pRec: 0.124

Intolerance Scores

• loftool: 0.197
• rvis_EVS: -0.47
• rvis_percentile_EVS: 23.43

Haploinsufficiency Scores

• pHI: 0.243
• hipred: Y
• hipred_score: 0.693
• ghis: 0.451

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.584

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Notum
• Phenotype: muscle phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); respiratory system phenotype; renal/urinary system phenotype; skeleton phenotype

Zebrafish Information Network

• Gene name: notum1a
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: curved

Gene ontology

• 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;protein depalmitoleylation
• Cellular component: extracellular region;endoplasmic reticulum lumen
• Molecular function: phospholipase C activity;palmitoleyl hydrolase activity