MEOX1

protein-coding

mesenchyme homeobox 1, the group of HOXL subclass homeoboxes

Gene summary

This gene encodes a member of a subfamily of non-clustered, diverged, antennapedia-like homeobox-containing genes. The encoded protein may play a role in the molecular signaling network regulating somite development. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

MANE transcript

NM_004527.4

Inheritance

AR, AD

ClinVar variants

P:7U:60B:47

Top phenotype

Klippel-Feil syndrome 2

gnomAD constraint

pLI —, LoF o/e 0.68

Max pathogenic AF

—

Genomic locus

chr17:43,640,389-43,661,922

External References & Databases

Ensembl (ENSG00000005102)

Transcript & Mutation Effects

hg38 • Region Span ~21.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Klippel-Feil syndrome 2, autosomal recessiveMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0008958

Submitter: Ambry Genetics

Klippel-Feil syndrome 2, autosomal recessiveSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008958

Submitter: G2P

Klippel-Feil syndrome 2, autosomal recessiveSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008958

Submitter: PanelApp Australia

Klippel-Feil syndrome 2, autosomal recessiveSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008958

Submitter: Labcorp Genetics (formerly Invitae)

isolated Klippel-Feil syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0016520

Submitter: Orphanet

Clinical Genomic Database (CGD)

Klippel-Feil syndrome 2AR

Manifestation: Musculoskeletal

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: 23290072; 24073994

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MEOX1 variants in ClinVar

5 Conditions Cataloged

not providedTotal: 91

Inborn genetic diseasesTotal: 45

MEOX1-related disorderTotal: 19

not specifiedTotal: 6

Klippel-Feil syndrome 2, autosomal recessiveTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004527.4. 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	37 clinvar	2 clinvar	40
missense		1 clinvar	58 clinvar	7 clinvar	1 clinvar	67
nonsense	1 clinvar	3 clinvar				4
start loss						0
frameshift	1 clinvar	1 clinvar	1 clinvar			3
splice donor/acceptor (+/-2bp)						0
Total	2	5	60	44	3	114

Highest pathogenic variant AF is 0.0000074381423

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004527.4	RefSeq	NP_004518.1	3	MANE Select
ENST00000318579.9	Ensembl	ENSP00000321684.4	3	MANE Select
NM_001040002.2	RefSeq	NP_001035091.1	3	Standard
NM_013999.4	RefSeq	NP_054705.1	2	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
meox1	Danio rerio	Structure: xanthophore Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

meox1

Danio rerio

Structure: xanthophore

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

somite specification
multicellular organism development
biological_process
positive regulation of transcription by RNA polymerase II
hematopoietic stem cell differentiation

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
molecular_function
chromatin binding
DNA-binding transcription factor activity

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000318579
Coding exons: 3
Length: 21567
Individuals with no LoFs: 125735
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125747
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.261	155	146	1.06	0.00000866	1633
Missense (PolyPhen)		37	42.833	0.86381		477
Synonymous	-0.279	65	62.2	1.04	0.00000386	516
Loss of Function	0.967	7	10.4	0.676	6.71e-7	105

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000063	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00017	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000045	0.000044	rare
South Asian	0.000034	0.000033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Mesodermal transcription factor that plays a key role in somitogenesis and is specifically required for sclerotome development. Required for maintenance of the sclerotome polarity and formation of the cranio-cervical joints (PubMed:23290072, PubMed:24073994). Binds specifically to the promoter of target genes and regulates their expression. Activates expression of NKX3-2 in the sclerotome. Activates expression of CDKN1A and CDKN2A in endothelial cells, acting as a regulator of vascular cell proliferation. While it activates CDKN1A in a DNA-dependent manner, it activates CDKN2A in a DNA-independent manner. Required for hematopoietic stem cell (HSCs) induction via its role in somitogenesis: specification of HSCs occurs via the deployment of a specific endothelial precursor population, which arises within a sub-compartment of the somite named endotome. {ECO:0000250|UniProtKB:F1Q4R9, ECO:0000250|UniProtKB:P32442, ECO:0000269|PubMed:23290072, ECO:0000269|PubMed:24073994}.;
Disease: DISEASE: Klippel-Feil syndrome 2, autosomal recessive (KFS2) [MIM:214300]: A skeletal disorder characterized by congenital fusion of cervical vertebrae. It is due to a failure in the normal segmentation of vertebrae during the early weeks of fetal development. The clinical triad consists of short neck, low posterior hairline, and limited neck movement. {ECO:0000269|PubMed:23290072, ECO:0000269|PubMed:24073994}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.105

Intolerance Scores

LoFtool: 0.137
RVIS EVS: 0.64
RVIS percentile EVS: 83.9

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.970

Gene Damage Prediction

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