SLC16A12

protein-coding

solute carrier family 16 member 12, the group of Solute carrier family 16

Gene summary

This gene encodes a transmembrane transporter that likely plays a role in monocarboxylic acid transport. A mutation in this gene has been associated with juvenile cataracts with microcornea and renal glucosuria. [provided by RefSeq, Mar 2010]

MANE transcript

NM_213606.4

Inheritance

ClinVar variants

P:3U:105B:24

Top phenotype

Cataract 47

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr10:89,430,299-89,556,641

External References & Databases

Ensembl (ENSG00000152779)

Transcript & Mutation Effects

hg38 • Region Span ~126.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

juvenile cataract-microcornea-renal glucosuria syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0012786

Submitter: Orphanet

juvenile cataract-microcornea-renal glucosuria syndromeLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0012786

Submitter: Laboratory for Molecular Medicine

This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.

juvenile cataract-microcornea-renal glucosuria syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0012786

Submitter: Labcorp Genetics (formerly Invitae)

juvenile cataract-microcornea-renal glucosuria syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0012786

Submitter: PanelApp Australia

juvenile cataract-microcornea-renal glucosuria syndromeLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0012786

Submitter: G2P

Clinical Genomic Database (CGD)

Cataract 47AD

Manifestation: Biochemical; Renal

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: 17458810; 18304496

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC16A12 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 66

Juvenile cataract-microcornea-renal glucosuria syndromeTotal: 60

not providedTotal: 41

SLC16A12-related disorderTotal: 13

Developmental cataractTotal: 1

Congenital ocular colobomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_213606.4. 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	15 clinvar		16
missense		1 clinvar	98 clinvar	8 clinvar	1 clinvar	108
nonsense	1 clinvar		2 clinvar			3
start loss			1 clinvar			1
frameshift		1 clinvar	2 clinvar			3
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	1	2	105	23	1	132

Highest pathogenic variant AF is 0.0000020521802

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 49 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_213606.4	RefSeq	NP_998771.3	6	MANE Select
ENST00000371790.5	Ensembl	ENSP00000360855.4	6	MANE Select
ENST00000475682.1	Ensembl	ENSP00000436965.1	1	Standard
ENST00000899673.1	Ensembl	ENSP00000569732.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Glycosphingolipid metabolism
Glycerophospholipid metabolism

Biological Process

monocarboxylic acid transport
creatine transmembrane transport

Molecular Function

creatine transmembrane transporter activity
monocarboxylic acid transmembrane transporter activity
symporter activity

Cellular Component

plasma membrane
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000371790
Coding exons: 6
Length: 126348
Individuals with no LoFs: 125725
Homozygous LoFs: 0
Heterozygous LoFs: 23
Defined: 125748
p: 0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.951	233	278	0.839	0.0000143	3323
Missense (PolyPhen)		84	120.48	0.69722		1457
Synonymous	0.545	98	105	0.932	0.00000570	1071
Loss of Function	3.20	4	19.1	0.209	8.15e-7	253

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00033	0.00033	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.000065	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Proton-linked monocarboxylate transporter that mediates creatine transport across the plasma membrane. {ECO:0000269|PubMed:23578822}.;

Recessive Scores

pRec: 0.121

Intolerance Scores

LoFtool: 0.726
RVIS EVS: -0.14
RVIS percentile EVS: 43.57

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0466

Gene Damage Prediction

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