POMP

proteasome maturation protein

Basic information

Region (hg38): 13:28659065-28678959

Previous symbols: [ "C13orf12" ]

Links

ENSG00000132963 ∙ NCBI:51371 ∙ OMIM:613386 ∙ HGNC:20330 ∙ Uniprot:Q9Y244 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• keratosis linearis-ichthyosis congenita-sclerosing keratoderma syndrome (Limited), mode of inheritance: AR
• keratosis linearis-ichthyosis congenita-sclerosing keratoderma syndrome (Moderate), mode of inheritance: AR
• proteasome-associated autoinflammatory syndrome 2 (Moderate), mode of inheritance: AD
• keratosis linearis-ichthyosis congenita-sclerosing keratoderma syndrome (Strong), mode of inheritance: AR
• keratosis linearis-ichthyosis congenita-sclerosing keratoderma syndrome (Supportive), mode of inheritance: AR
• proteasome-associated autoinflammatory syndrome 2 (Strong), mode of inheritance: AD
• keratosis linearis-ichthyosis congenita-sclerosing keratoderma syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Proteasome-associated autoinflammatory syndrome 2	AD	Allergy/Immunology/Infectious	Individuals have been described with recurrent infections, and awareness may allow preventative measures and early and aggressive treatment of infections; HSCT has been described	Allergy/Immunology/Infectious; Craniofacial; Dermatologic; Musculoskeletal	12022327; 20226437; 26524591; 29805043

ClinVar

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

• Keratosis linearis-ichthyosis congenita-sclerosing keratoderma syndrome (2 variants)
• Proteasome-associated autoinflammatory syndrome 2 (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POMP 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			1	19	1	21
missense			39			39
nonsense						0
start loss						0
frameshift	1	1				2
inframe indel			1			1
splice donor/acceptor (+/-2bp)			2			2
splice region			6	7		13
non coding	1		1	15	8	25
Total	2	1	44	34	9

Highest pathogenic variant AF is 0.0000985

Variants in POMP

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

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

Position	Type	Phenotype	Significance	ClinVar
13-28659088-TC-T		Keratosis linearis-ichthyosis congenita-sclerosing keratoderma syndrome	Pathogenic (Aug 23, 2023)
13-28659090-C-T			Uncertain significance (Oct 05, 2023)
13-28659190-G-C			Uncertain significance (Jul 12, 2023)
13-28659191-A-G			Uncertain significance (Oct 23, 2023)
13-28659194-G-A			Likely benign (Nov 28, 2023)
13-28659200-C-T			Likely benign (Nov 14, 2023)
13-28659201-C-T			Likely benign (May 08, 2023)
13-28659206-G-C			Benign (Jan 31, 2024)
13-28662209-A-T			Benign (Nov 12, 2018)
13-28662352-C-T		not specified	Benign (Nov 12, 2023)
13-28662390-GT-G			Benign (Aug 15, 2022)
13-28662399-T-C			Likely benign (Oct 07, 2022)
13-28662403-G-A			Likely benign (Nov 16, 2022)
13-28662423-T-C		Inborn genetic diseases	Uncertain significance (Aug 23, 2023)
13-28662430-TGAGCTAAAG-T			Uncertain significance (May 08, 2023)
13-28662444-G-A			Uncertain significance (Nov 08, 2023)
13-28662448-T-G			Uncertain significance (Mar 29, 2022)
13-28662449-C-T			Uncertain significance (Sep 15, 2021)
13-28662451-A-C			Likely benign (Nov 02, 2023)
13-28662451-A-T			Likely benign (Jan 13, 2022)
13-28662456-C-T			Uncertain significance (Sep 01, 2022)
13-28662464-T-C			Uncertain significance (Dec 12, 2023)
13-28662467-G-T			Uncertain significance (Apr 24, 2023)
13-28662473-G-A			Uncertain significance (May 24, 2023)
13-28662489-A-C		Inborn genetic diseases • POMP-related disorder	Uncertain significance (May 24, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POMP	protein_coding	protein_coding	ENST00000380842	6	19822

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.909	0.0900	122223	0	1	122224	0.00000409

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.966	49	72.1	0.680	0.00000354	923
Missense in Polyphen		7	14.424	0.48531		189
Synonymous	-0.118	26	25.2	1.03	0.00000125	263
Loss of Function	2.58	0	7.74	0.00	3.26e-7	101

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000295	0.0000295
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Molecular chaperone essential for the assembly of standard proteasomes and immunoproteasomes. Degraded after completion of proteasome maturation. Mediates the association of 20S preproteasome with the endoplasmic reticulum. {ECO:0000269|PubMed:15944226, ECO:0000269|PubMed:16251969, ECO:0000269|PubMed:17948026}.
• Disease: DISEASE: Keratosis linearis with ichthyosis congenita and sclerosing keratoderma (KLICK) [MIM:601952]: A keratinizing disorder characterized by ichthyosis, palmoplantar keratoderma with constricting bands around fingers, flexural deformities of fingers and keratotic papules in a linear distribution on the flexural side of large joints. Histological examination of the skin of affected individuals shows hypertrophy and hyperplasia of the spinous, granular and horny epidermal layer. {ECO:0000269|PubMed:20226437}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Proteasome - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.102

Intolerance Scores

• rvis_EVS: -0.19
• rvis_percentile_EVS: 39.68

Haploinsufficiency Scores

• pHI: 0.275
• hipred: Y
• hipred_score: 0.825
• ghis: 0.675

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.508

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pomp

Gene ontology

• Biological process: proteasome assembly
• Cellular component: nucleus;cytoplasm;endoplasmic reticulum;cytosol;nuclear speck;organelle membrane
• Molecular function: protein binding