POMP

protein-coding

proteasome maturation protein

Gene summary

The protein encoded by this gene is a molecular chaperone that binds 20S preproteasome components and is essential for 20S proteasome formation. The 20S proteasome is the proteolytically active component of the 26S proteasome complex. The encoded protein is degraded before the maturation of the 20S proteasome is complete. A variant in the 5' UTR of this gene has been associated with KLICK syndrome, a rare skin disorder.[provided by RefSeq, Aug 2010]

Previous symbols:

C13orf12

MANE transcript

NM_015932.6

Inheritance

AR, AD

ClinVar variants

P:5U:66B:21

Top phenotype

Proteasome-associated autoinflammatory syndrome 2

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr13:28,659,065-28,678,959

External References & Databases

Ensembl (ENSG00000132963)

Transcript & Mutation Effects

hg38 • Region Span ~19.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

keratosis linearis-ichthyosis congenita-sclerosing keratoderma syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011169

Submitter: Orphanet

keratosis linearis-ichthyosis congenita-sclerosing keratoderma syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0011169

Submitter: G2P

keratosis linearis-ichthyosis congenita-sclerosing keratoderma syndromeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0011169

Submitter: Ambry Genetics

proteasome-associated autoinflammatory syndrome 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0054700

Submitter: Labcorp Genetics (formerly Invitae)

keratosis linearis-ichthyosis congenita-sclerosing keratoderma syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011169

Submitter: Labcorp Genetics (formerly Invitae)

proteasome-associated autoinflammatory syndrome 2MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0054700

Submitter: Ambry Genetics

proteasome-associated autoinflammatory syndrome 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0054700

Submitter: PanelApp Australia

keratosis linearis-ichthyosis congenita-sclerosing keratoderma syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011169

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Proteasome-associated autoinflammatory syndrome 2AD

Manifestation: Allergy/Immunology/Infectious; Craniofacial; Dermatologic; Musculoskeletal

Intervention: Allergy/Immunology/Infectious

Rationale: Individuals have been described with recurrent infections, and awareness may allow preventative measures and early and aggressive treatment of infections; HSCT has been described

Refs: 12022327; 20226437; 26524591; 29805043

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to POMP variants in ClinVar

6 Conditions Cataloged

not providedTotal: 129

Inborn genetic diseasesTotal: 22

not specifiedTotal: 12

Proteasome-associated autoinflammatory syndrome 2Total: 6

POMP-related disorderTotal: 4

Keratosis linearis-ichthyosis congenita-sclerosing keratoderma syndromeTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015932.6. 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			1 clinvar	20 clinvar	1 clinvar	22
missense			60 clinvar			60
nonsense						0
start loss						0
frameshift	3 clinvar	1 clinvar	1 clinvar			5
splice donor/acceptor (+/-2bp)		1 clinvar	4 clinvar			5
Total	3	2	66	20	1	92

Highest pathogenic variant AF is 0.0000034512034

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015932.6	RefSeq	NP_057016.1	6	MANE Select
ENST00000380842.5	Ensembl	ENSP00000370222.4	6	MANE Select
ENST00000460403.1	Ensembl	ENSP00000492579.1	3	Standard
ENST00000460403.2	Ensembl	ENSP00000492579.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Proteasome - Homo sapiens (human)

Biological Process

proteasome assembly

Molecular Function

protein binding

Cellular Component

nucleus
cytoplasm
endoplasmic reticulum
cytosol
nuclear speck

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000380842
Coding exons: 6
Length: 19822
Individuals with no LoFs: 122223
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 122224
p: 0.00000409

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.966	49	72.1	0.680	0.00000354	923
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000030	0.000030	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.102

Intolerance Scores

RVIS EVS: -0.19
RVIS percentile EVS: 39.68

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.508

Gene Damage Prediction

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