PAM

peptidylglycine alpha-amidating monooxygenase

Basic information

Region (hg38): 5:102753980-103029730

Links

ENSG00000145730 ∙ NCBI:5066 ∙ OMIM:170270 ∙ HGNC:8596 ∙ Uniprot:P19021 ∙ 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 PAM gene.

• Inborn genetic diseases (24 variants)
• not provided (15 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PAM 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				5	3	8
missense			24	1	4	29
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					2	2
non coding						0
Total	0	0	24	6	7

Variants in PAM

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

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

Position	Type	Phenotype	Significance	ClinVar
5-102867275-T-A			Benign (Aug 18, 2018)
5-102867328-G-C			Benign (Dec 31, 2019)
5-102867355-G-A		not specified	Uncertain significance (Dec 28, 2023)
5-102901384-G-A		not specified	Uncertain significance (Aug 09, 2021)
5-102914002-T-C		not specified	Uncertain significance (Feb 28, 2023)
5-102925031-G-A			Likely benign (May 15, 2018)
5-102925040-A-G		not specified	Uncertain significance (Apr 13, 2023)
5-102926580-T-C			Benign (May 23, 2018)
5-102926666-G-C		not specified	Uncertain significance (Jul 27, 2021)
5-102946885-C-T			Benign (Jun 20, 2018)
5-102949575-C-A		not specified	Uncertain significance (Nov 21, 2022)
5-102949581-C-A		not specified	Uncertain significance (Dec 15, 2023)
5-102949583-T-A		not specified	Uncertain significance (Feb 28, 2023)
5-102950766-T-G		not specified	Uncertain significance (Jun 10, 2022)
5-102959909-A-G		not specified	Uncertain significance (Jan 31, 2023)
5-102960019-C-T			Benign (Jun 20, 2018)
5-102961171-A-G			Likely benign (Jun 14, 2018)
5-102961218-T-G		not specified	Uncertain significance (Jul 25, 2023)
5-102961219-G-T			Likely benign (Jul 06, 2018)
5-102974125-A-G		not specified	Uncertain significance (Mar 14, 2023)
5-102974349-T-G		not specified	Uncertain significance (Jun 01, 2023)
5-102974426-A-C			Benign (Jun 20, 2018)
5-102990287-A-C		not specified	Uncertain significance (Jul 09, 2021)
5-102990304-G-C		not specified	Uncertain significance (Sep 17, 2021)
5-103003091-A-G		not specified	Uncertain significance (Jun 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PAM	protein_coding	protein_coding	ENST00000304400	25	277125

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000693	1.00	125698	0	50	125748	0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.960	464	526	0.882	0.0000260	6387
Missense in Polyphen		260	301.72	0.86173		3776
Synonymous	0.567	174	184	0.947	0.00000916	1858
Loss of Function	4.38	19	53.6	0.355	0.00000273	646

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000182	0.000181
Ashkenazi Jewish	0.000503	0.000496
East Asian	0.000164	0.000163
Finnish	0.0000929	0.0000924
European (Non-Finnish)	0.000283	0.000281
Middle Eastern	0.000164	0.000163
South Asian	0.0000981	0.0000980
Other	0.000166	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Bifunctional enzyme that catalyzes 2 sequential steps in C-terminal alpha-amidation of peptides. The monooxygenase part produces an unstable peptidyl(2-hydroxyglycine) intermediate that is dismutated to glyoxylate and the corresponding desglycine peptide amide by the lyase part. C-terminal amidation of peptides such as neuropeptides is essential for full biological activity.

Recessive Scores

• pRec: 0.271

Intolerance Scores

• loftool: 0.191
• rvis_EVS: -0.33
• rvis_percentile_EVS: 30.86

Haploinsufficiency Scores

• pHI: 0.588
• hipred: Y
• hipred_score: 0.706
• ghis: 0.436

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.856

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pam
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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; embryo phenotype

Zebrafish Information Network

• Gene name: pam
• Affected structure: brush border epithelial cell
• Phenotype tag: abnormal
• Phenotype quality: absent

Gene ontology

• Biological process: peptide amidation;response to hypoxia;long-chain fatty acid metabolic process;regulation of transcription by RNA polymerase II;central nervous system development;heart development;lactation;response to pH;toxin metabolic process;protein amidation;ovulation cycle process;response to estradiol;regulation of actin cytoskeleton organization;odontogenesis;response to drug;response to copper ion;regulation of protein secretion;protein homooligomerization;response to glucocorticoid;oxidation-reduction process;maternal process involved in female pregnancy;limb development
• Cellular component: extracellular region;trans-Golgi network;plasma membrane;cell surface;membrane;integral component of membrane;secretory granule membrane;neuron projection;perikaryon;perinuclear region of cytoplasm;extracellular exosome
• Molecular function: peptidylglycine monooxygenase activity;peptidylamidoglycolate lyase activity;copper ion binding;calcium ion binding;protein binding;zinc ion binding;protein kinase binding;L-ascorbic acid binding