LRMDA

Summary

LRMDA (leucine rich melanocyte differentiation associated, HGNC:23405) is a protein-coding gene on chromosome 10q22.2-q22.3, encoding Leucine-rich melanocyte differentiation-associated protein (Q9H2I8). Required for melanocyte differentiation.

This gene encodes a leucine-rich repeat protein. The encoded protein is thought to play a role in melanocyte differentiation. Mutations in this gene have been associated with autosomal recessive oculocutaneous albinism 7 (OCA7). Alternatively spliced transcript variants have been identified.

Source: NCBI Gene 83938 — RefSeq curated summary.

At a glance

• Gene–disease (curated): oculocutaneous albinism type 7 (Strong, GenCC)
• GWAS associations: 42
• Clinical variants (ClinVar): 99 total — 6 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 9
• MANE Select transcript: NM_001305581

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23405
Approved symbol	LRMDA
Name	leucine rich melanocyte differentiation associated
Location	10q22.2-q22.3
Locus type	gene with protein product
Status	Approved
Aliases	CDA017, OCA7
Ensembl gene	ENSG00000148655
Ensembl biotype	protein_coding
OMIM	614537
Entrez	83938

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 12 protein_coding_CDS_not_defined, 3 protein_coding

ENST00000372499, ENST00000468134, ENST00000483375, ENST00000488655, ENST00000488759, ENST00000493194, ENST00000493690, ENST00000496424, ENST00000593699, ENST00000593817, ENST00000595936, ENST00000596228, ENST00000597823, ENST00000598708, ENST00000611255

RefSeq mRNA: 2 — MANE Select: NM_001305581 NM_001305581, NM_032024

CCDS: CCDS7351, CCDS76319

Canonical transcript exons

ENST00000611255 — 7 exons

Exon	Start	End
ENSE00003492576	76058666	76058783
ENSE00003581825	76036008	76036134
ENSE00003627095	76047164	76047303
ENSE00003690164	76324401	76324485
ENSE00003742703	75431624	75431754
ENSE00003744090	75438394	75438494
ENSE00003850631	76557209	76560168

Expression profiles

Bgee: expression breadth ubiquitous, 208 present calls, max score 96.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.2748 / max 200.6655, expressed in 1190 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105631	6.5435	1158
105630	0.4846	155
105648	0.0615	20
105634	0.0599	23
105652	0.0568	10
105635	0.0381	12
105650	0.0202	8
105649	0.0101	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	96.18	gold quality
right adrenal gland cortex	UBERON:0035827	96.15	gold quality
left adrenal gland cortex	UBERON:0035825	95.53	gold quality
right adrenal gland	UBERON:0001233	95.48	gold quality
adrenal cortex	UBERON:0001235	95.31	gold quality
left adrenal gland	UBERON:0001234	95.30	gold quality
adrenal gland	UBERON:0002369	95.08	gold quality
right atrium auricular region	UBERON:0006631	93.69	gold quality
cardiac atrium	UBERON:0002081	93.18	gold quality
pancreatic ductal cell	CL:0002079	92.92	silver quality
sural nerve	UBERON:0015488	91.93	gold quality
adrenal tissue	UBERON:0018303	91.02	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.73	gold quality
bone marrow cell	CL:0002092	89.63	gold quality
apex of heart	UBERON:0002098	89.42	gold quality
monocyte	CL:0000576	89.19	gold quality
leukocyte	CL:0000738	88.93	gold quality
right lobe of liver	UBERON:0001114	88.81	gold quality
spleen	UBERON:0002106	88.55	gold quality
kidney epithelium	UBERON:0004819	88.19	silver quality
C1 segment of cervical spinal cord	UBERON:0006469	88.09	gold quality
heart	UBERON:0000948	87.75	gold quality
left ventricle myocardium	UBERON:0006566	87.56	gold quality
heart left ventricle	UBERON:0002084	87.55	gold quality
liver	UBERON:0002107	87.50	gold quality
thyroid gland	UBERON:0002046	87.19	gold quality
ascending aorta	UBERON:0001496	87.14	gold quality
left lobe of thyroid gland	UBERON:0001120	87.12	gold quality
cardiac ventricle	UBERON:0002082	87.06	gold quality
thoracic aorta	UBERON:0001515	87.04	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-HCAD-30	yes	4886.35
E-GEOD-180759	yes	4366.61
E-HCAD-35	yes	3766.24
E-MTAB-11268	yes	3116.44
E-HCAD-25	yes	1978.88
E-CURD-119	yes	29.82
E-ANND-3	yes	13.37
E-ANND-2	no	3767.41
E-GEOD-109979	no	80.08
E-GEOD-81608	no	7.87
E-MTAB-7606	no	4.50

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA3, TP63

Literature-anchored findings (GeneRIF, showing 1)

• This finding suggests that haploinsufficiency of C10orf11 contributes to the cognitive defects in 10q22 deletion patients. (PMID:19844253)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrmda	ENSDARG00000057166
mus_musculus	Lrmda	ENSMUSG00000063458
rattus_norvegicus	Lrmda	ENSRNOG00000069198
drosophila_melanogaster	MESK4	FBGN0043069
drosophila_melanogaster	CG31274	FBGN0051274

Paralogs (2): SNRPA1 (ENSG00000131876), LRRC72 (ENSG00000205858)

Protein

Protein identifiers

Leucine-rich melanocyte differentiation-associated protein — Q9H2I8 (reviewed: Q9H2I8)

All UniProt accessions (3): Q9H2I8, A0A087WWI0, M0R2H0

UniProt curated annotations — full annotation on UniProt →

Function. Required for melanocyte differentiation.

Tissue specificity. In the embryo, expressed in melanoblasts. In the fetus, expressed in melanocytes. Not detected in retinal pigment epithelial cells.

Disease relevance. Albinism, oculocutaneous, 7 (OCA7) [MIM:615179] A disorder of pigmentation characterized by reduced biosynthesis of melanin in the skin, hair and eyes. Patients show reduced or lacking pigmentation associated with classic albinism ocular abnormalities, including decreased visual acuity, macular hypoplasia, optic dysplasia, atypical choroidal vessels, and nystagmus. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (2): NP_001292510, NP_114413 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR043313	LRMDA	Family

Pfam: PF14580

UniProt features (7 total): repeat 4, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H2I8-F1	78.40	0.40

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 140 (showing top): GCANCTGNY_MYOD_Q6, RACCACAR_AML_Q6, CHANDRAN_METASTASIS_DN, EFC_Q6, GOBP_PIGMENTATION, PAX8_B, IRF7_01, AML_Q6, TGCTGAY_UNKNOWN, INGRAM_SHH_TARGETS_UP, GOBP_PIGMENT_CELL_DIFFERENTIATION, OCT1_06, TGACATY_UNKNOWN, GOBP_DEVELOPMENTAL_PIGMENTATION, AFP1_Q6

GO Biological Process (2): melanocyte differentiation (GO:0030318), cell differentiation (GO:0030154)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
pigment cell differentiation	1
cellular developmental process	1
binding	1

Protein interactions and networks

STRING

1158 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRMDA	SLC24A5	Q71RS6	773
LRMDA	OCA2	Q04671	708
LRMDA	SLC45A2	Q9UMX9	704
LRMDA	GPR143	P51810	620
LRMDA	HPS6	Q86YV9	601
LRMDA	TYRP1	P17643	593
LRMDA	HPS5	Q9UPZ3	591
LRMDA	SPATA9	Q9BWV2	581
LRMDA	HPS4	Q9NQG7	581
LRMDA	TYR	P14679	580
LRMDA	HPS3	Q969F9	577
LRMDA	BLOC1S3	Q6QNY0	571
LRMDA	CCDC172	P0C7W6	568
LRMDA	BLOC1S6	Q9UL45	524
LRMDA	THSD4	Q6ZMP0	515

IntAct

0 interactions, top by confidence:

BioGRID (7): C10orf11 (Two-hybrid), C10orf11 (Two-hybrid), C10orf11 (Two-hybrid), RABIF (Two-hybrid), C10orf11 (Affinity Capture-MS), C10orf11 (Proximity Label-MS), C10orf11 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0JM56, A2RRS8, A6H759, A6NJI9, A6PVS8, B0FXQ5, B1ANS9, B7FF12, D3ZXS4, D4A039, E9QA62, F1MCA7, O00522, P62046, P70587, Q0V9Y8, Q0VAK6, Q14DL3, Q3U3V8, Q3UMG5, Q3V0L5, Q4KLV2, Q5JTW2, Q5PPX0, Q5SUS0, Q5VUJ6, Q6AXZ2, Q6AYL8, Q6GQN5, Q6IRU7, Q6P5J6, Q7Z3E5, Q7ZV84, Q80TE7, Q80TM9, Q8BGI7, Q8BVU0, Q8C008, Q8C0Q4, Q8C5W4

Diamond homologs: B6CZ61, P09661, P43333, P57784, Q3SZC6, Q4P5F9, Q4R8Y8, Q4WV66, Q5A449, Q5BGW9, Q5EAD8, Q6A1I3, Q6BT60, Q6C417, Q6YSF3, Q755D2, Q7S9P4, Q9BLB6, Q9D9B4, Q9H2I8, Q9SCQ7, Q9USX8, Q9V4Q8, Q28XE2, Q6FV04, Q92688, Q9V895, O35381, P39687, P49911, P51122, Q0P5X1, Q5ZMN0, Q64G17, Q6PAF6, Q7ZUP0, Q86QS6, Q8HY67, Q9D3R3, Q9EST5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	5
Uncertain significance	26
Likely benign	43
Benign	10

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
1013286	NM_001305581.2(LRMDA):c.583del (p.Glu195fs)	Pathogenic
1994322	NM_001305581.2(LRMDA):c.624C>A (p.Tyr208Ter)	Pathogenic
2175083	NM_001305581.2(LRMDA):c.620dup (p.Tyr208fs)	Pathogenic
3245012	NC_000010.10:g.(?77795746)(77818561_?)del	Pathogenic
3688733	NM_001305581.2(LRMDA):c.661dup (p.Ile221fs)	Pathogenic
41917	NM_001305581.2(LRMDA):c.150dup (p.Ala51fs)	Pathogenic
209972	NM_001305581.2(LRMDA):c.351C>A (p.Asn117Lys)	Likely pathogenic
2102118	NM_001305581.2(LRMDA):c.398+1G>C	Likely pathogenic
2859805	NM_001305581.2(LRMDA):c.398+2_398+13del	Likely pathogenic
3713869	NM_001305581.2(LRMDA):c.259-2del	Likely pathogenic
41916	NM_001305581.2(LRMDA):c.664C>T (p.Arg222Ter)	Likely pathogenic

SpliceAI

1888 predictions. Top by Δscore:

Variant	Effect	Δscore
10:75785254:T:TA	acceptor_gain	0.9900
10:75808282:G:T	donor_gain	0.9900
10:75814064:A:AG	acceptor_gain	0.9900
10:75814065:G:GG	acceptor_gain	0.9900
10:75874111:G:GA	donor_gain	0.9900
10:75782839:GTTTT:G	donor_gain	0.9800
10:75782806:T:G	donor_gain	0.9700
10:75786663:G:GT	donor_gain	0.9700
10:75808282:G:GT	donor_gain	0.9600
10:75796195:T:A	acceptor_gain	0.9500
10:75874110:T:TA	donor_gain	0.9500
10:75785268:ATAAT:A	acceptor_gain	0.9400
10:75808297:GC:G	donor_gain	0.9400
10:75827599:T:A	donor_gain	0.9000
10:75915232:TTC:T	donor_gain	0.9000
10:75783018:AAAAG:A	donor_loss	0.8900
10:75783019:AAAG:A	donor_loss	0.8900
10:75783020:AAGG:A	donor_loss	0.8900
10:75783021:AG:A	donor_loss	0.8900
10:75783022:GG:G	donor_loss	0.8900
10:75783023:GTT:G	donor_loss	0.8900
10:75783024:T:A	donor_loss	0.8900
10:75785259:T:TA	acceptor_gain	0.8900
10:75798412:C:CG	donor_gain	0.8900
10:75798412:C:G	donor_gain	0.8900
10:75863544:TCA:T	donor_gain	0.8900
10:75882782:GT:G	donor_gain	0.8900
10:75796193:A:AG	acceptor_gain	0.8800
10:75796277:A:T	donor_gain	0.8800
10:75808298:C:G	donor_gain	0.8800

AlphaMissense

1466 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:76047227:A:C	S80R	0.998
10:76047229:T:A	S80R	0.998
10:76047229:T:G	S80R	0.998
10:76036049:T:C	L30P	0.997
10:76047241:C:A	N84K	0.997
10:76047241:C:G	N84K	0.997
10:76058674:T:A	V108D	0.997
10:76058700:T:C	F117L	0.997
10:76058702:T:A	F117L	0.997
10:76058702:T:G	F117L	0.997
10:76557265:T:C	F192L	0.997
10:76557267:T:A	F192L	0.997
10:76557267:T:G	F192L	0.997
10:76036121:T:C	L54P	0.996
10:76036131:C:A	N57K	0.996
10:76036131:C:G	N57K	0.996
10:76047225:T:C	L79P	0.996
10:76047231:T:C	L81P	0.996
10:76058695:T:G	L115W	0.996
10:76036049:T:A	L30H	0.995
10:76036115:T:C	L52S	0.995
10:76058695:T:C	L115S	0.995
10:76058704:T:C	L118P	0.995
10:76557269:T:C	I193T	0.994
10:76047225:T:A	L79H	0.993
10:76036121:T:A	L54H	0.992
10:76557269:T:A	I193N	0.992
10:76047299:T:G	Y104D	0.991
10:76557261:C:A	N190K	0.991
10:76557261:C:G	N190K	0.991

dbSNP variants (sampled 300 via entrez): RS1000001485 (10:75798561 A>T), RS1000003889 (10:76431744 C>T), RS1000006010 (10:75783366 G>A), RS1000006169 (10:76100530 A>T), RS1000012338 (10:76249987 G>A), RS1000012901 (10:75934185 T>G), RS1000013154 (10:75740597 G>A,C), RS1000013169 (10:76184009 A>C), RS1000016128 (10:75618140 GTTGT>G), RS1000016303 (10:76125859 C>A), RS1000018169 (10:76038813 C>G), RS1000019549 (10:75701391 A>C), RS1000023144 (10:75994083 A>C), RS1000024068 (10:76297306 T>C), RS1000025308 (10:75998458 TC>T)

Disease associations

OMIM: gene MIM:614537 | disease phenotypes: MIM:615179

GenCC curated gene-disease

Disease	Classification	Inheritance
oculocutaneous albinism type 7	Strong	Autosomal recessive

Mondo (1): oculocutaneous albinism type 7 (MONDO:0014070)

Orphanet (1): Oculocutaneous albinism type 7 (Orphanet:352745)

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000565	Esotropia
HP:0000577	Exotropia
HP:0000613	Photophobia
HP:0000639	Nystagmus
HP:0001022	Albinism
HP:0007663	Reduced visual acuity
HP:0008499	High hypermetropia
HP:0012805	Iris transillumination defect

GWAS associations

42 associations (top):

Study	Trait	p-value
GCST000523_1	Methotrexate pharmacokinetics (acute lymphoblastic leukemia)	7.000000e-06
GCST001251_10	Pulmonary function	3.000000e-12
GCST001357_1	Response to tamoxifen in breast cancer	6.000000e-09
GCST001784_30	Pulmonary function (smoking interaction)	5.000000e-08
GCST002113_2	Pulmonary function	2.000000e-06
GCST003983_21	Male-pattern baldness	2.000000e-12
GCST003989_42	Chin dimples	4.000000e-09
GCST004183_31	Lung function (FEV1)	5.000000e-08
GCST004184_17	Lung function (FVC)	4.000000e-07
GCST005116_13	Male-pattern baldness	9.000000e-24
GCST006061_119	Atrial fibrillation	1.000000e-11
GCST006291_23	Spherical equivalent or myopia (age of diagnosis)	4.000000e-08
GCST006414_2	Atrial fibrillation	7.000000e-10
GCST006463_18	Urinary albumin excretion (no hypertensive medication)	6.000000e-10
GCST006586_29	Urinary albumin excretion	1.000000e-13
GCST006661_174	Male-pattern baldness	1.000000e-11
GCST006661_248	Male-pattern baldness	2.000000e-24
GCST006979_591	Heel bone mineral density	1.000000e-11
GCST006979_592	Heel bone mineral density	6.000000e-18
GCST007429_142	Lung function (FVC)	2.000000e-21
GCST007430_117	Peak expiratory flow	4.000000e-10
GCST007431_158	Lung function (FEV1/FVC)	3.000000e-15
GCST007432_189	FEV1	4.000000e-34
GCST007692_27	Chronic obstructive pulmonary disease	2.000000e-06
GCST007692_65	Chronic obstructive pulmonary disease	3.000000e-10
GCST007847_96	Type 2 diabetes	2.000000e-09
GCST008662_8	Lung function in never smokers (low FEV1 vs high FEV1)	6.000000e-06
GCST008664_12	Lung function (low FEV1 vs high FEV1)	1.000000e-08
GCST008758_8	Pre-treatment viral load in HIV-1 infection	2.000000e-16
GCST008790_38	Urinary albumin-to-creatinine ratio	1.000000e-12

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0004314	forced expiratory volume
EFO:0004713	FEV/FVC ratio
EFO:0004312	vital capacity
EFO:0004847	age at onset
EFO:0004285	albuminuria
EFO:0009270	heel bone mineral density
EFO:0009718	peak expiratory flow
EFO:0010125	viral load
EFO:0007778	urinary albumin to creatinine ratio
EFO:0005665	white matter hyperintensity measurement
EFO:0004531	urate measurement
EFO:0004980	appendicular lean mass
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs10509373	Efficacy	3	tamoxifen	Breast Neoplasms

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs10509373	LRMDA	3	3.75	1	tamoxifen

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	10
Aflatoxin B1	affects expression, decreases expression, increases methylation	7
Valproic Acid	affects expression, decreases expression, increases expression	5
lasiocarpine	decreases expression	2
methyleugenol	decreases expression	2
N-Nitrosopyrrolidine	decreases expression	2
Quercetin	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	increases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
perfluorooctanoic acid	increases expression	1
benzo(e)pyrene	increases methylation	1
entinostat	increases expression	1
clothianidin	decreases expression	1
abrine	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Vorinostat	increases expression	1
Acetaminophen	decreases expression	1
Ethanol	increases expression	1
Arsenic	affects methylation	1
Cisplatin	decreases expression	1
Methapyrilene	increases methylation	1
Mustard Gas	decreases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	decreases expression	1

Clinical trials (associated diseases)

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