MLPH

melanophilin, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 2:237485428-237555322

Links

ENSG00000115648 ∙ NCBI:79083 ∙ OMIM:606526 ∙ HGNC:29643 ∙ Uniprot:Q9BV36 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Griscelli syndrome type 3 (Strong), mode of inheritance: AR
• Griscelli syndrome type 3 (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Griscelli syndrome, type 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	12148598; 12897212

ClinVar

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

• not provided (2 variants)
• Griscelli syndrome type 3 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MLPH 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				22	10	32
missense		2	49	8	11	70
nonsense	1					1
start loss						0
frameshift	1	1	1			3
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1				1
splice region			1	6	1	8
non coding			1	12	43	56
Total	2	4	52	42	64

Highest pathogenic variant AF is 0.0000197

Variants in MLPH

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

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

Position	Type	Phenotype	Significance	ClinVar
2-237493141-A-G			Benign (Nov 12, 2018)
2-237493448-T-C		Inborn genetic diseases	Uncertain significance (May 26, 2024)
2-237493465-A-G		MLPH-related disorder	Benign (Dec 24, 2023)
2-237493496-C-T		Griscelli syndrome type 3	Pathogenic (Jan 24, 2024)
2-237493523-G-A			Uncertain significance (Oct 18, 2023)
2-237493529-C-T		Griscelli syndrome type 3	Likely pathogenic (Apr 04, 2024)
2-237493530-G-A		Griscelli syndrome type 3	Likely pathogenic (Aug 31, 2022)
2-237493547-C-T			Likely benign (Jan 02, 2024)
2-237493550-G-C			Benign (Oct 27, 2022)
2-237510595-G-A		MLPH-related disorder	Benign (Jan 22, 2024)
2-237510643-C-T			Benign (Jan 08, 2024)
2-237510646-G-A			Likely benign (Jun 13, 2018)
2-237510678-A-G			Benign (Jan 08, 2024)
2-237510703-G-C		Inborn genetic diseases	Uncertain significance (Mar 19, 2024)
2-237510743-C-T		Inborn genetic diseases	Likely benign (Nov 17, 2022)
2-237510744-G-A			Uncertain significance (Sep 24, 2021)
2-237510754-G-A		MLPH-related disorder	Likely benign (Sep 08, 2024)
2-237510755-G-A		Inborn genetic diseases	Conflicting classifications of pathogenicity (Nov 27, 2023)
2-237510755-G-T		Griscelli syndrome type 3	Pathogenic (May 23, 2022)
2-237510758-G-A		Inborn genetic diseases	Uncertain significance (May 31, 2022)
2-237510777-AC-A			Pathogenic (Oct 29, 2023)
2-237510796-G-T		Griscelli syndrome type 3	Likely pathogenic (Sep 25, 2019)
2-237510968-A-G		Griscelli syndrome type 3	Benign (Sep 05, 2021)
2-237510979-G-A		not specified	Benign (Jan 29, 2024)
2-237510992-C-T		MLPH-related disorder	Likely benign (Sep 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MLPH	protein_coding	protein_coding	ENST00000264605	15	69891

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.38e-10	0.941	125702	0	46	125748	0.000183

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.124	347	341	1.02	0.0000215	3873
Missense in Polyphen		76	76.497	0.99351		889
Synonymous	-0.104	148	146	1.01	0.0000101	1188
Loss of Function	2.00	20	32.3	0.619	0.00000175	383

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000422	0.000422
Ashkenazi Jewish	0.00	0.00
East Asian	0.000381	0.000381
Finnish	0.00	0.00
European (Non-Finnish)	0.000178	0.000176
Middle Eastern	0.000381	0.000381
South Asian	0.000261	0.000261
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Rab effector protein involved in melanosome transport. Serves as link between melanosome-bound RAB27A and the motor protein MYO5A. {ECO:0000269|PubMed:12062444}.
• Disease: DISEASE: Griscelli syndrome 3 (GS3) [MIM:609227]: Rare autosomal recessive disorder characterized by pigmentary dilution of the skin and hair, the presence of large clumps of pigment in hair shafts, and an accumulation of melanosomes in melanocytes, without other clinical manifestations. {ECO:0000269|PubMed:12897212}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Deregulation of Rab and Rab Effector Genes in Bladder Cancer (Consensus)

Recessive Scores

• pRec: 0.185

Intolerance Scores

• loftool: 0.808
• rvis_EVS: 0.49
• rvis_percentile_EVS: 79.62

Haploinsufficiency Scores

• pHI: 0.492
• hipred: N
• hipred_score: 0.314
• ghis: 0.386

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.704

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mlph
• 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); homeostasis/metabolism phenotype; pigmentation phenotype; vision/eye phenotype

Zebrafish Information Network

• Gene name: mlpha
• Affected structure: melanocyte
• Phenotype tag: abnormal
• Phenotype quality: aggregated

Gene ontology

• Biological process: intracellular protein transport;melanosome transport
• Cellular component: dendrite;cortical actin cytoskeleton;perinuclear region of cytoplasm;extracellular exosome
• Molecular function: actin binding;protein binding;myosin binding;Rab GTPase binding;protein binding, bridging;metal ion binding