LHX6
protein-codingLIM homeobox 6, the group of LIM class homeoboxes
Gene summary
This gene encodes a member of a large protein family that contains the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein has tandem LIM domains as well as a DNA-binding homeodomain. The protein functions as a transcription factor involved in embryogenesis and head development and is highly expressed in neural crest derived mesenchyme cells. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2017]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~27.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0005090
Submitter: Labcorp Genetics (formerly Invitae)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to LHX6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014368.5. 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 | 0 | |||||
| missense | 40 | 40 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 43 | 0 | 0 | 43 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055183.2 | 10 | MANE Select | |
| Ensembl | ENSP00000377854.4 | 10 | MANE Select | |
| RefSeq | NP_001229262.1 | 9 | Standard | |
| RefSeq | NP_001229263.1 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- regulation of transcription by RNA polymerase II
- cerebral cortex radially oriented cell migration
- cerebral cortex tangential migration
- cerebral cortex GABAergic interneuron migration
- cell maturation
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription factor activity
- protein binding
- sequence-specific DNA binding
- metal ion binding
Cellular Component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000394319
- Coding exons
- 10
- Length
- 27050
- Individuals with no LoFs
- 124269
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 124270
- p
- 0.00000402
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.93 | 104 | 228 | 0.455 | 0.0000122 | 2522 |
| Missense (PolyPhen) | 24 | 90.152 | 0.26622 | 913 | ||
| Synonymous | 1.01 | 88 | 101 | 0.872 | 0.00000591 | 770 |
| Loss of Function | 3.65 | 2 | 19.3 | 0.104 | 8.80e-7 | 227 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Probable transcription factor required for the expression of a subset of genes involved in interneurons migration and development. Functions in the specification of cortical interneuron subtypes and in the migration of GABAergic interneuron precursors from the subpallium to the cerebral cortex (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.148
Intolerance Scores
- LoFtool
- 0.0293
- RVIS EVS
- 0.19
- RVIS percentile EVS
- 66.82
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.911
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |