LRMDA

protein-coding

leucine rich melanocyte differentiation associated, the group of MicroRNA protein coding host genes

Gene summary

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. [provided by RefSeq, Mar 2015]

Previous symbols:

C10orf11

MANE transcript

NM_001305581.2

Inheritance

ClinVar variants

P:13U:35B:40

Top phenotype

Albinism, oculocutaneous, type VII

gnomAD constraint

pLI —, LoF o/e 0.64

Max pathogenic AF

—

Genomic locus

chr10:75,431,624-76,560,168

External References & Databases

Ensembl (ENSG00000148655)

Transcript & Mutation Effects

hg38 • Region Span ~1,128.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

oculocutaneous albinism type 7SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014070

Submitter: Orphanet

oculocutaneous albinism type 7STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014070

Submitter: PanelApp Australia

oculocutaneous albinism type 7STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014070

Submitter: Labcorp Genetics (formerly Invitae)

oculocutaneous albinism type 7STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014070

Submitter: G2P

Clinical Genomic Database (CGD)

Albinism, oculocutaneous, type VIIAR

Manifestation: Dermatologic; Ophthalmologic

Intervention: General

Rationale: 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

Refs: 23395477

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LRMDA variants in ClinVar

7 Conditions Cataloged

not providedTotal: 114

not specifiedTotal: 8

LRMDA-related disorderTotal: 6

Oculocutaneous albinism type 7Total: 5

Inborn genetic diseasesTotal: 3

C10ORF11 & LRMDA-related disordersTotal: 3

LRMDA-related disordersTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001305581.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	34 clinvar	2 clinvar	37
missense		1 clinvar	32 clinvar	1 clinvar	3 clinvar	37
nonsense	2 clinvar	2 clinvar				4
start loss			1 clinvar			1
frameshift	4 clinvar					4
splice donor/acceptor (+/-2bp)		4 clinvar	1 clinvar			5
Total	6	7	35	35	5	88

Highest pathogenic variant AF is 0.00027137445

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001305581.2	RefSeq	NP_001292510.1	7	MANE Select
ENST00000611255.5	Ensembl	ENSP00000480240.1	7	MANE Select
NM_032024.5	RefSeq	NP_114413.1	6	Standard
ENST00000372499.5	Ensembl	ENSP00000361577.1	6	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
lrmda	Danio rerio	Structure: melanocyte Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

lrmda

Danio rerio

Structure: melanocyte

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

melanocyte differentiation

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000372499
Coding exons: 6
Length: 958928
Individuals with no LoFs: 125713
Homozygous LoFs: 0
Heterozygous LoFs: 35
Defined: 125748
p: 0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.115	112	109	1.03	0.00000584	1271
Missense (PolyPhen)		31	29.613	1.0468		399
Synonymous	-0.792	55	48.0	1.15	0.00000291	381
Loss of Function	1.11	7	11.0	0.638	6.09e-7	137

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00021	0.00021	rare
South Asian	0.000066	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for melanocyte differentiation. {ECO:0000269|PubMed:23395477}.;
Disease: DISEASE: 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. {ECO:0000269|PubMed:23395477}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.0845

Intolerance Scores

RVIS EVS: 0.17
RVIS percentile EVS: 65.56

Essentials

Essential (gene trap): N