PMEL

premelanosome protein

Basic information

Region (hg38): 12:55954104-55973317

Previous symbols: [ "SIL", "SILV" ]

Links

ENSG00000185664 ∙ NCBI:6490 ∙ OMIM:155550 ∙ HGNC:10880 ∙ Uniprot:P40967 ∙ 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 PMEL gene.

• Inborn genetic diseases (15 variants)
• not provided (12 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PMEL 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				3	1	4
missense			14	1	7	22
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	14	4	8

Variants in PMEL

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

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

Position	Type	Phenotype	Significance	ClinVar
12-55954267-A-T		not specified	Uncertain significance (Feb 05, 2024)
12-55954313-C-G		not specified	Uncertain significance (Sep 22, 2023)
12-55954322-G-A			Likely benign (Mar 29, 2018)
12-55954347-C-T		not specified	Uncertain significance (Mar 07, 2024)
12-55955270-T-TTACCTATATATATATATA			Benign (May 21, 2018)
12-55955337-A-G			Benign (Jul 31, 2018)
12-55955344-C-T		not specified	Uncertain significance (Apr 28, 2022)
12-55955547-C-A		not specified	Uncertain significance (Apr 04, 2023)
12-55955821-C-T		not specified	Uncertain significance (Dec 20, 2021)
12-55955822-C-T			Benign (Jul 31, 2018)
12-55955823-G-A		PMEL-related disorder	Likely benign (Feb 21, 2023)
12-55955827-G-A		not specified	Uncertain significance (Jun 13, 2023)
12-55955846-C-G		not specified	Uncertain significance (Aug 02, 2021)
12-55956109-T-C		not specified	Uncertain significance (Oct 05, 2023)
12-55956121-C-T		not specified	Uncertain significance (Jul 13, 2022)
12-55956963-G-A			Benign (Mar 29, 2018)
12-55957041-G-C		not specified	Uncertain significance (Aug 16, 2022)
12-55957045-T-G		not specified	Uncertain significance (Apr 06, 2023)
12-55957080-A-G		not specified	Likely benign (Sep 14, 2023)
12-55957101-G-A		not specified	Uncertain significance (May 04, 2023)
12-55957193-C-G			Benign (Dec 31, 2019)
12-55957216-G-A			Benign (May 30, 2018)
12-55957218-G-A			Benign (Mar 01, 2018)
12-55957274-T-C			Likely benign (Mar 28, 2018)
12-55957383-G-T		not specified	Uncertain significance (Nov 17, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PMEL	protein_coding	protein_coding	ENST00000449260	11	19213

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.06e-18	0.00883	125594	0	154	125748	0.000613

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.894	322	370	0.869	0.0000186	4260
Missense in Polyphen		123	140.9	0.87297		1724
Synonymous	-0.132	148	146	1.01	0.00000747	1473
Loss of Function	0.310	28	29.8	0.939	0.00000153	307

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00110	0.00110
Ashkenazi Jewish	0.000894	0.000893
East Asian	0.000109	0.000109
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000916	0.000915
Middle Eastern	0.000109	0.000109
South Asian	0.000392	0.000392
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a central role in the biogenesis of melanosomes. Involved in the maturation of melanosomes from stage I to II. The transition from stage I melanosomes to stage II melanosomes involves an elongation of the vesicle, and the appearance within of distinct fibrillar structures. Release of the soluble form, ME20-S, could protect tumor cells from antibody mediated immunity. {ECO:0000269|PubMed:11694580, ECO:0000269|PubMed:21962903}.

Recessive Scores

• pRec: 0.319

Intolerance Scores

• rvis_EVS: -0.04
• rvis_percentile_EVS: 50.51

Haploinsufficiency Scores

• pHI: 0.530
• hipred: N
• hipred_score: 0.123
• ghis: 0.395

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pmel
• Phenotype: pigmentation phenotype; vision/eye phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: pmelb
• Affected structure: retinal pigmented epithelium
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: melanosome organization;melanin biosynthetic process
• Cellular component: extracellular region;endoplasmic reticulum membrane;Golgi apparatus;plasma membrane;integral component of plasma membrane;multivesicular body membrane;melanosome
• Molecular function: protein binding;identical protein binding