MLPH

Summary

MLPH (melanophilin, HGNC:29643) is a protein-coding gene on chromosome 2q37.3, encoding Melanophilin (Q9BV36). Rab effector protein involved in melanosome transport.

This gene encodes a member of the exophilin subfamily of Rab effector proteins. The protein forms a ternary complex with the small Ras-related GTPase Rab27A in its GTP-bound form and the motor protein myosin Va. A similar protein complex in mouse functions to tether pigment-producing organelles called melanosomes to the actin cytoskeleton in melanocytes, and is required for visible pigmentation in the hair and skin. A mutation in this gene results in Griscelli syndrome type 3, which is characterized by a silver-gray hair color and abnormal pigment distribution in the hair shaft. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 79083 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Griscelli syndrome type 3 (Strong, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 286 total — 3 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 10
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_024101

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29643
Approved symbol	MLPH
Name	melanophilin
Location	2q37.3
Locus type	gene with protein product
Status	Approved
Aliases	l1Rk3, l(1)-3Rk, Slac-2a, ln, exophilin-3, SLAC2-A
Ensembl gene	ENSG00000115648
Ensembl biotype	protein_coding
OMIM	606526
Entrez	79083

Gene structure

Transcript identifiers

Ensembl transcripts: 64 — 51 protein_coding, 8 retained_intron, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000264605, ENST00000338530, ENST00000409373, ENST00000410032, ENST00000415753, ENST00000422695, ENST00000429898, ENST00000432475, ENST00000434770, ENST00000436965, ENST00000437893, ENST00000464123, ENST00000468178, ENST00000469619, ENST00000477222, ENST00000477457, ENST00000477501, ENST00000478712, ENST00000482528, ENST00000485956, ENST00000489967, ENST00000494110, ENST00000495439, ENST00000872925, ENST00000872926, ENST00000872927, ENST00000872928, ENST00000872929, ENST00000872930, ENST00000872931, ENST00000872932, ENST00000872933, ENST00000872934, ENST00000872935, ENST00000872936, ENST00000872937, ENST00000917527, ENST00000917528, ENST00000917529, ENST00000951127, ENST00000951128, ENST00000951129, ENST00000951130, ENST00000951131, ENST00000951132, ENST00000951133, ENST00000951134, ENST00000951135, ENST00000951136, ENST00000951137, ENST00000951138, ENST00000951139, ENST00000951140, ENST00000951141, ENST00000951142, ENST00000951143, ENST00000951144, ENST00000951145, ENST00000951146, ENST00000951147, ENST00000951148, ENST00000951149, ENST00000951150, ENST00000951151

RefSeq mRNA: 4 — MANE Select: NM_024101 NM_001042467, NM_001281473, NM_001281474, NM_024101

CCDS: CCDS2518, CCDS42836, CCDS63172, CCDS63173

Canonical transcript exons

ENST00000264605 — 16 exons

Exon	Start	End
ENSE00001510390	237553566	237555322
ENSE00001708032	237487251	237487437
ENSE00003461580	237534564	237534647
ENSE00003500889	237546606	237546683
ENSE00003518544	237510989	237511101
ENSE00003522707	237493403	237493536
ENSE00003547569	237527377	237527516
ENSE00003562776	237519910	237520029
ENSE00003564428	237552337	237552437
ENSE00003573480	237540348	237540533
ENSE00003633886	237518539	237518648
ENSE00003643523	237525601	237525805
ENSE00003660074	237540802	237540957
ENSE00003676410	237542567	237542659
ENSE00003687318	237510574	237510795
ENSE00003691084	237549221	237549278

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 99.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.0588 / max 479.7404, expressed in 1078 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
26255	26.4632	1075
26253	0.4531	158
26254	0.1425	91

Top tissues by expression

287 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	99.74	gold quality
parotid gland	UBERON:0001831	99.32	gold quality
right uterine tube	UBERON:0001302	98.91	gold quality
endocervix	UBERON:0000458	98.26	gold quality
right lung	UBERON:0002167	98.02	gold quality
saliva-secreting gland	UBERON:0001044	97.95	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.77	gold quality
minor salivary gland	UBERON:0001830	97.72	gold quality
nasal cavity epithelium	UBERON:0005384	97.60	gold quality
apex of heart	UBERON:0002098	97.28	gold quality
prostate gland	UBERON:0002367	97.16	gold quality
pylorus	UBERON:0001166	97.14	gold quality
ectocervix	UBERON:0012249	97.10	gold quality
epithelium of bronchus	UBERON:0002031	97.08	gold quality
upper lobe of left lung	UBERON:0008952	97.03	gold quality
gall bladder	UBERON:0002110	97.02	gold quality
bronchus	UBERON:0002185	96.94	gold quality
upper lobe of lung	UBERON:0008948	96.91	gold quality
bronchial epithelial cell	CL:0002328	96.86	gold quality
right lobe of thyroid gland	UBERON:0001119	96.69	gold quality
nasal cavity mucosa	UBERON:0001826	96.22	gold quality
left lobe of thyroid gland	UBERON:0001120	96.13	gold quality
right atrium auricular region	UBERON:0006631	96.09	gold quality
cardiac atrium	UBERON:0002081	95.67	gold quality
thyroid gland	UBERON:0002046	95.59	gold quality
ileal mucosa	UBERON:0000331	95.49	gold quality
right lobe of liver	UBERON:0001114	95.42	gold quality
rectum	UBERON:0001052	95.19	gold quality
mucosa of transverse colon	UBERON:0004991	94.85	gold quality
body of stomach	UBERON:0001161	94.82	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-MTAB-8221	yes	261.92
E-MTAB-9841	yes	229.73
E-HCAD-1	yes	79.33
E-CURD-114	yes	51.51
E-GEOD-135922	yes	30.06
E-GEOD-125970	yes	20.82
E-GEOD-130148	yes	12.18
E-CURD-122	yes	8.80
E-ENAD-27	yes	4.16
E-MTAB-7249	no	154.03
E-GEOD-99795	no	109.29
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

68 targeting MLPH, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-892A	99.54	68.16	1141
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-532-3P	99.34	65.76	1195
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-4685-5P	99.25	65.99	1563

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 17)

• Slac2-a/melanophilin contains an N-terminal Slp homology domain (SHD) (PMID: 11327731). The SHD of Slac2-a specifically and directly binds the GTP-bound form of Rab27A and Rab27B (PMID: 11773082). The C-terminus of Slac2-a directly binds myosin Va. (PMID:11856727)
• Slac2-a/melanophilin, the missing link between Rab27 and myosin Va: implications of a tripartite protein complex for melanosome transport (PMID:11856727)
• links rab27a and myosin Va function in melanosome transport (PMID:11980908)
• Melanophilin has a role in bridging Rab27a on melanosomes and myosin Va on actin filaments during melanosome transport. (PMID:12062444)
• SHD1 of Slac2-a/melanophilin alone is both necessary and sufficient for high affinity specific recognition of the GTP-bound form of Rab27A (PMID:12189142)
• The C-terminus of Slac2-a/melanophilin contains a novel actin-binding site, which may be involved in capture of Rab27-containing organelles in the actin-enriched cell periphery. (PMID:12221080)
• Griscelli syndrome restricted to hypopigmentation results from a melanophilin defect (GS3) or a MYO5A F-exon deletion (GS1). (PMID:12897212)
• deletion 2q37.3 is implicated in autism (PMID:15517821)
• The pathologic defect in Griscelli syndrome 3 came from the MLPH R35W substitution, which induced aggregation of melanosomes in the perinuclear area of melanocytes because of failure to interact with RAB27A. (PMID:21883982)
• The results showed that Rab27A(Q78L) is unable to localize on mature melanosomes and that its inhibitory activity on melanosome transport is completely dependent on its binding to the Rab27A effector Slac2-a/melanophilin. (PMID:24584932)
• These results unravel a hidden link between AR and a functional putative PCa risk SNP, whose allele alteration affects androgen regulation of its host gene MLPH. (PMID:26411452)
• A novel Rab27a mutation binds melanophilin, but not Munc13-4, causing immunodeficiency without albinism. (PMID:27016801)
• we detected two potential associations with well-recognized skin cancer risk traits that modify miRNA-mRNA interactions: rs2325814 in the 3’UTR of the MLPH gene and rs752107 in the 3’UTR of the WNT3A gene. (PMID:28266728)
• Kinase fusions involving MYO5A and TPM3 have been reported in Spitz tumors, and our series adds MLPH to this group. (PMID:30857967)
• This study provides strong evidence showing that prostate cancer risk Single-nucleotide polymorphism rs13426236 upregulates expression of MLPH transcript V4, which may function as a candidate oncogene in prostate cancer. (PMID:31659808)
• RAB27A/Melanophilin Blocker Inhibits Melanoma Cell Motility and Invasion. (PMID:31978414)
• MLPH is a novel adipogenic factor controlling redox homeostasis to inhibit lipid peroxidation in adipocytes. (PMID:39083977)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mlphb	ENSDARG00000062481
danio_rerio	mlpha	ENSDARG00000070991
mus_musculus	Mlph	ENSMUSG00000026303
rattus_norvegicus	Mlph	ENSRNOG00000019763

Paralogs (2): MOBP (ENSG00000168314), MYRIP (ENSG00000170011)

Protein

Protein identifiers

Melanophilin — Q9BV36 (reviewed: Q9BV36)

Alternative names: Exophilin-3, Slp homolog lacking C2 domains a, Synaptotagmin-like protein 2a

All UniProt accessions (8): Q9BV36, C9JI01, C9JKV5, H7C052, H7C190, H7C2D8, H7C371, H7C3K9

UniProt curated annotations — full annotation on UniProt →

Function. Rab effector protein involved in melanosome transport. Serves as link between melanosome-bound RAB27A and the motor protein MYO5A.

Subunit / interactions. Binds RAB27A that has been activated by GTP-binding via its N-terminus. Binds MYO5A via its C-terminal coiled coil domain.

Subcellular location. Cytoplasm.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9BV36-1	1	yes
Q9BV36-2	2
Q9BV36-3	3
Q9BV36-4	4
Q9BV36-5	5

RefSeq proteins (4): NP_001035932, NP_001268402, NP_001268403, NP_077006* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006788	Myrip/Melanophilin	Domain
IPR010911	Rab_BD	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR037442	Melanophilin_FYVE-rel_dom	Domain
IPR041282	FYVE_2	Domain
IPR051745	Intracell_Transport_Effector	Family

Pfam: PF02318, PF04698

UniProt features (33 total): sequence variant 9, splice variant 6, sequence conflict 4, region of interest 4, compositionally biased region 3, mutagenesis site 3, chain 1, domain 1, zinc finger region 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BV36-F1	61.58	0.25

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (3):

Position	Phenotype
14	abolishes rab27a binding.
24	decreases rab27a binding.
32	abolishes rab27a binding.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-9824585	Regulation of MITF-M-dependent genes involved in pigmentation
R-HSA-1266738	Developmental Biology
R-HSA-9730414	MITF-M-regulated melanocyte development
R-HSA-9856651	MITF-M-dependent gene expression

MSigDB gene sets: 180 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, BENPORATH_ES_WITH_H3K27ME3, GOBP_PIGMENT_GRANULE_LOCALIZATION, GOBP_VESICLE_LOCALIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, GOZGIT_ESR1_TARGETS_DN, GOBP_CELLULAR_PIGMENTATION, GOMF_GTPASE_BINDING, GOBP_PIGMENTATION, WEI_MYCN_TARGETS_WITH_E_BOX, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM5, SMID_BREAST_CANCER_LUMINAL_B_UP, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP, MCBRYAN_PUBERTAL_BREAST_5_6WK_UP

GO Biological Process (2): intracellular protein transport (GO:0006886), melanosome transport (GO:0032402)

GO Molecular Function (7): actin binding (GO:0003779), zinc ion binding (GO:0008270), myosin binding (GO:0017022), protein-macromolecule adaptor activity (GO:0030674), small GTPase binding (GO:0031267), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (6): cytosol (GO:0005829), dendrite (GO:0030425), cortical actin cytoskeleton (GO:0030864), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
MITF-M-dependent gene expression	1
Developmental Biology	1
MITF-M-regulated melanocyte development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoskeletal protein binding	2
cytoplasm	2
intracellular protein localization	1
protein transport	1
intracellular transport	1
melanosome localization	1
establishment of melanosome localization	1
pigment granule transport	1
transition metal ion binding	1
protein binding	1
molecular adaptor activity	1
GTPase binding	1
binding	1
cation binding	1
neuron projection	1
dendritic tree	1
actin cytoskeleton	1
cortical cytoskeleton	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

474 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MLPH	RAB27A	P51159	999
MLPH	MYO5A	Q9Y4I1	999
MLPH	RAB27B	O00194	941
MLPH	SYTL2	Q9HCH5	941
MLPH	EXPH5	Q8NEV8	850
MLPH	RPH3A	Q9Y2J0	812
MLPH	MREG	Q8N565	807
MLPH	RAB3A	P20336	790
MLPH	SYTL1	Q8IYJ3	662
MLPH	TRIM3	O75382	649
MLPH	RAB8A	P24407	643
MLPH	CHML	P26374	642
MLPH	MYO7A	P78427	626
MLPH	RAP2B	P17964	581
MLPH	UNC13D	Q70J99	579

IntAct

37 interactions, top by confidence:

A	B	Type	Score
MLPH	RAB27A	psi-mi:“MI:0915”(physical association)	0.830
RAB27A	MLPH	psi-mi:“MI:0915”(physical association)	0.830
MLPH	RAB27A	psi-mi:“MI:0914”(association)	0.830
RAB27A	MLPH	psi-mi:“MI:0407”(direct interaction)	0.830
RAB27B	MLPH	psi-mi:“MI:0915”(physical association)	0.740
C1orf216	MLPH	psi-mi:“MI:0915”(physical association)	0.560
RECK	MLPH	psi-mi:“MI:0915”(physical association)	0.560
MLPH	BLOC1S6	psi-mi:“MI:0915”(physical association)	0.560
RAB27B	GBA1	psi-mi:“MI:0914”(association)	0.530
MLPH	Rab27b	psi-mi:“MI:0407”(direct interaction)	0.440
Rab27a	MLPH	psi-mi:“MI:0407”(direct interaction)	0.440
MLPH	RAB27A	psi-mi:“MI:0915”(physical association)	0.400
ACTA1	RAB27A	psi-mi:“MI:0915”(physical association)	0.400
MLPH		psi-mi:“MI:0915”(physical association)	0.370
CUL2	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
BMI1	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
BTRC	ACOT7	psi-mi:“MI:0914”(association)	0.350
SNAP91	GMNN	psi-mi:“MI:0914”(association)	0.350
ADD3	ADD1	psi-mi:“MI:0914”(association)	0.350
RAB27A	GTPBP1	psi-mi:“MI:0914”(association)	0.350
RAB27A	ATE1	psi-mi:“MI:0914”(association)	0.350
RAB27B	MYH7B	psi-mi:“MI:0914”(association)	0.350
SNAP91	PIK3C2A	psi-mi:“MI:0914”(association)	0.350

BioGRID (38): MLPH (Affinity Capture-MS), MLPH (Affinity Capture-RNA), MLPH (Affinity Capture-MS), RAB27A (Affinity Capture-Western), MYO5A (Affinity Capture-Western), ACTA1 (Affinity Capture-Western), MLPH (Affinity Capture-Western), MLPH (Reconstituted Complex), MLPH (Protein-RNA), MLPH (Two-hybrid), MLPH (Two-hybrid), RECK (Two-hybrid), C1orf216 (Two-hybrid), MLPH (Reconstituted Complex), MLPH (Reconstituted Complex)

ESM2 similar proteins: A2A7Y5, A2A9F4, A2ALU4, A2RU30, A2VE02, A6NGG8, A6NMK8, B1AXH1, B2RQL2, D2J0Y4, M3WHG5, Q08DN6, Q0VET5, Q14B48, Q2NL68, Q2YDE2, Q4V8B5, Q5DTX6, Q5JTC6, Q5JXC2, Q5RCQ2, Q5SX79, Q5XIK6, Q66JV7, Q6AY88, Q6AYH0, Q6GQV1, Q6NS69, Q6P1D7, Q6PAC4, Q6ZRS4, Q76N32, Q7TP36, Q7TSA6, Q7Z591, Q80VW7, Q811R2, Q86YN6, Q8BP99, Q8C0C4

Diamond homologs: A8T6P4, M3WHG5, Q13875, Q63327, Q7TNY7, Q8K3I4, Q8NFW9, Q8VHQ7, Q91V27, Q96C24, Q9BV36, Q9D2P8, Q9R0Q1, Q4VX76, Q80T23, Q812E4, Q8TDW5, A0FGR8, A6QP06, A8KBH6, O00443, O00750, P05126, P05128, P05129, P05130, P05771, P05772, P10102, P10829, P20444, P21521, P24505, P24506, P34693, P47708, P47709, P63318, P63319, P68403

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

286 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	5
Uncertain significance	105
Likely benign	71
Benign	65

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
1686914	NM_024101.7(MLPH):c.292G>T (p.Glu98Ter)	Pathogenic
191315	NM_024101.7(MLPH):c.987del (p.Lys330fs)	Pathogenic
2772757	NM_024101.7(MLPH):c.318del (p.Cys107fs)	Pathogenic
1324723	NM_024101.7(MLPH):c.332+1G>T	Likely pathogenic
3721570	NM_024101.7(MLPH):c.110+2T>C	Likely pathogenic
3891697	NM_024101.7(MLPH):c.963_966del (p.Ala321_His322insTer)	Likely pathogenic
4268	NM_024101.7(MLPH):c.103C>T (p.Arg35Trp)	Likely pathogenic
4739770	NM_024101.7(MLPH):c.1021-1G>A	Likely pathogenic

SpliceAI

2657 predictions. Top by Δscore:

Variant	Effect	Δscore
2:237493400:CAG:C	acceptor_loss	1.0000
2:237493402:G:GC	acceptor_loss	1.0000
2:237493517:A:T	donor_gain	1.0000
2:237493527:A:T	donor_gain	1.0000
2:237493533:TAGAG:T	donor_loss	1.0000
2:237493534:AGAG:A	donor_loss	1.0000
2:237493535:GA:G	donor_gain	1.0000
2:237493535:GAGT:G	donor_loss	1.0000
2:237493536:AG:A	donor_loss	1.0000
2:237493537:G:GG	donor_gain	1.0000
2:237493537:G:T	donor_loss	1.0000
2:237493538:T:G	donor_loss	1.0000
2:237493539:G:GC	donor_loss	1.0000
2:237493540:A:AT	donor_loss	1.0000
2:237493541:G:C	donor_loss	1.0000
2:237510571:AAG:A	acceptor_gain	1.0000
2:237511100:AG:A	donor_loss	1.0000
2:237511101:GG:G	donor_loss	1.0000
2:237511102:G:T	donor_loss	1.0000
2:237511103:T:A	donor_loss	1.0000
2:237518644:GCAAA:G	donor_gain	1.0000
2:237518649:G:GG	donor_gain	1.0000
2:237519908:A:G	acceptor_gain	1.0000
2:237540346:AG:A	acceptor_gain	1.0000
2:237540347:GG:G	acceptor_gain	1.0000
2:237542644:G:GT	donor_gain	1.0000
2:237546602:CCAG:C	acceptor_loss	1.0000
2:237546603:CA:C	acceptor_loss	1.0000
2:237546604:A:AT	acceptor_loss	1.0000
2:237546605:G:GA	acceptor_loss	1.0000

AlphaMissense

3901 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:237493497:G:C	R24P	0.994
2:237511041:T:C	F129L	0.994
2:237511043:C:A	F129L	0.994
2:237511043:C:G	F129L	0.994
2:237511050:T:C	F132L	0.992
2:237511052:C:A	F132L	0.992
2:237511052:C:G	F132L	0.992
2:237493469:G:C	A15P	0.991
2:237493500:A:C	D25A	0.991
2:237493509:T:C	L28P	0.991
2:237493479:T:A	V18D	0.990
2:237493491:T:A	V22D	0.990
2:237493455:T:C	L10P	0.989
2:237493500:A:T	D25V	0.989
2:237493501:T:A	D25E	0.989
2:237493501:T:G	D25E	0.989
2:237511014:T:A	W120R	0.989
2:237511014:T:C	W120R	0.989
2:237511016:G:C	W120C	0.988
2:237511016:G:T	W120C	0.988
2:237542591:G:C	A491P	0.987
2:237493499:G:C	D25H	0.986
2:237511042:T:C	F129S	0.986
2:237542594:G:C	A492P	0.986
2:237542598:T:C	L493P	0.985
2:237493500:A:G	D25G	0.984
2:237511017:T:G	Y121D	0.984
2:237493455:T:A	L10H	0.983
2:237493512:G:C	R29P	0.983
2:237510655:C:G	C64W	0.978

dbSNP variants (sampled 300 via entrez): RS1000076319 (2:237496323 C>T), RS1000129199 (2:237526653 G>A,C), RS1000144191 (2:237485565 C>T), RS1000175801 (2:237485765 A>G), RS1000208736 (2:237526929 A>G), RS1000249351 (2:237485290 T>G), RS1000279081 (2:237521084 G>A), RS1000418712 (2:237490700 A>G), RS1000463357 (2:237554194 G>A,C), RS1000485746 (2:237486865 A>G), RS1000517894 (2:237487081 C>A,T), RS1000529115 (2:237537547 G>C), RS1000530073 (2:237524099 G>A), RS1000542559 (2:237529137 G>A), RS1000642164 (2:237505681 T>C)

Disease associations

OMIM: gene MIM:606526 | disease phenotypes: MIM:609227

GenCC curated gene-disease

Disease	Classification	Inheritance
Griscelli syndrome type 3	Strong	Autosomal recessive

Mondo (1): Griscelli syndrome type 3 (MONDO:0012220)

Orphanet (2): Griscelli syndrome (Orphanet:381), Griscelli syndrome type 3 (Orphanet:79478)

HPO phenotypes

10 total (10 of 10 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000707	Abnormality of the nervous system
HP:0002218	Silver-gray hair
HP:0002227	White eyelashes
HP:0002721	Immunodeficiency
HP:0004527	Large clumps of pigment irregularly distributed along hair shaft
HP:0005599	Hypopigmentation of hair
HP:0007443	Partial albinism
HP:0007730	Iris hypopigmentation
HP:0011463	Childhood onset

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001147_5	Prostate cancer	4.000000e-08
GCST005580_11	Intraocular pressure	6.000000e-15
GCST005580_241	Intraocular pressure	1.000000e-16
GCST006288_508	Heel bone mineral density	3.000000e-09
GCST006979_96	Heel bone mineral density	5.000000e-22
GCST90000654_8	Central corneal thickness	3.000000e-08
GCST90013466_68	Height	2.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0009270	heel bone mineral density
EFO:0005213	central corneal thickness

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537303	Griscelli syndrome type 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

63 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, increases expression	4
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression, increases methylation	4
Estradiol	affects binding, increases expression, affects cotreatment	3
Temozolomide	affects response to substance, decreases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Genistein	increases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
sotorasib	affects cotreatment, decreases expression	1
methyleugenol	increases expression	1
lead acetate	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
trichostatin A	increases expression	1
arsenite	decreases methylation	1
o,p’-DDT	increases expression	1
cupric chloride	increases expression	1
1-nitropyrene	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dimethylarsinous acid	decreases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
jinfukang	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.