GPNMB

glycoprotein nmb

Basic information

Region (hg38): 7:23235967-23275108

Links

ENSG00000136235

∙ NCBI:10457 ∙ OMIM:604368 ∙ HGNC:4462 ∙ Uniprot:Q14956 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

amyloidosis, primary localized cutaneous, 3 (Moderate), mode of inheritance: AR
amyloidosis, primary localized cutaneous, 3 (Strong), mode of inheritance: AR
amyloidosis, primary localized cutaneous, 3 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Amyloidosis, primary, localized cutaneous, 3	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Dermatologic	19416385; 29336782

ClinVar

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

Inborn_genetic_diseases (72 variants)
not_provided (20 variants)
Amyloidosis,_primary_localized_cutaneous,_3 (15 variants)
GPNMB-related_disorder (11 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GPNMB gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002510.3. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				6 clinvar	4 clinvar	10
missense			64 clinvar	10 clinvar	4 clinvar	78
nonsense	3 clinvar	2 clinvar		1 clinvar		6
start loss						0
frameshift	5 clinvar	2 clinvar				7
splice donor/acceptor (+/-2bp)	1 clinvar	2 clinvar				3
Total	9	6	64	17	8

Highest pathogenic variant AF is 0.000725067

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GPNMB	protein_coding	protein_coding	ENST00000381990	11	39142

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.88e-27	0.00000806	125403	1	344	125748	0.00137

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.124	318	324	0.981	0.0000173	3752
Missense in Polyphen		86	91.99	0.93489		1142
Synonymous	0.116	130	132	0.987	0.00000804	1124
Loss of Function	-1.35	36	28.2	1.27	0.00000161	302

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00230	0.00230
Ashkenazi Jewish	0.00179	0.00179
East Asian	0.00402	0.00398
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.00133	0.00133
Middle Eastern	0.00402	0.00398
South Asian	0.000922	0.000882
Other	0.000816	0.000815

dbNSFP

Source: dbNSFP

Function: FUNCTION: Could be a melanogenic enzyme. {ECO:0000250}.;
Disease: DISEASE: Note=Increased expression levels in glioblastoma multiforme biopsy samples correlate with poor patient survival prognosis (PubMed:16609006). Has been proposed as a potential target for antibodies coupled to cytotoxic drugs in the context of cancer immunotherapy, including that of melanoma (PubMed:16489096). {ECO:0000269|PubMed:16489096, ECO:0000269|PubMed:16609006}.; DISEASE: Amyloidosis, primary localized cutaneous, 3 (PLCA3) [MIM:617920]: A primary amyloidosis characterized by localized cutaneous amyloid deposition. This condition usually presents with itching (especially on the lower legs) and visible changes of skin hyperpigmentation and thickening that may be exacerbated by chronic scratching and rubbing. Primary localized cutaneous amyloidosis is often divided into macular and lichen subtypes although many affected individuals often show both variants coexisting. Lichen amyloidosis characteristically presents as a pruritic eruption of grouped hyperkeratotic papules with a predilection for the shins, calves, ankles and dorsa of feet and thighs. Papules may coalesce to form hyperkeratotic plaques that can resemble lichen planus, lichen simplex or nodular prurigo. Macular amyloidosis is characterized by small pigmented macules that may merge to produce macular hyperpigmentation, sometimes with a reticulate or rippled pattern. In macular and lichen amyloidosis, amyloid is deposited in the papillary dermis in association with grouped colloid bodies, thought to represent degenerate basal keratinocytes. The amyloid deposits probably reflect a combination of degenerate keratin filaments, serum amyloid P component, and deposition of immunoglobulins. PLCA3 inheritance is autosomal recessive. {ECO:0000269|PubMed:29336782}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Signaling by PTK6;Signal Transduction;PTK6 promotes HIF1A stabilization;Signaling by Non-Receptor Tyrosine Kinases (Consensus)

Recessive Scores

pRec: 0.135

Intolerance Scores

loftool: 0.984
rvis_EVS: 0.89
rvis_percentile_EVS: 89.29

Haploinsufficiency Scores

pHI: 0.702
hipred: N
hipred_score: 0.180
ghis: 0.445

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.186

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Gpnmb
Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; neoplasm; pigmentation phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; homeostasis/metabolism phenotype; immune system phenotype;

Gene ontology

Biological process: osteoblast differentiation;negative regulation of cytokine production;positive regulation of protein phosphorylation;cell adhesion;signal transduction;cell-cell signaling;negative regulation of cell population proliferation;regulation of signaling receptor activity;bone mineralization;positive regulation of cell migration;positive regulation of protein autophosphorylation;negative regulation of tumor necrosis factor production;regulation of tissue remodeling;negative regulation of T cell proliferation;regulation of angiogenesis;negative regulation of T cell activation;positive chemotaxis;positive regulation of ERK1 and ERK2 cascade;negative regulation of neuron death;negative regulation of G1/S transition of mitotic cell cycle
Cellular component: plasma membrane;integral component of plasma membrane;integral component of membrane;early endosome membrane;melanosome membrane
Molecular function: integrin binding;protein binding;heparin binding;chemoattractant activity;syndecan binding;receptor ligand activity