MEOX1

mesenchyme homeobox 1, the group of HOXL subclass homeoboxes

Basic information

Region (hg38): 17:43640388-43661922

Links

ENSG00000005102 ∙ NCBI:4222 ∙ OMIM:600147 ∙ HGNC:7013 ∙ Uniprot:P50221 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Klippel-Feil syndrome 1, autosomal dominant (Strong), mode of inheritance: AR
• Klippel-Feil syndrome 2, autosomal recessive (Moderate), mode of inheritance: AR
• Klippel-Feil syndrome 2, autosomal recessive (Strong), mode of inheritance: AR
• isolated Klippel-Feil syndrome (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Klippel-Feil syndrome 2	AR	General	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	Musculoskeletal	23290072; 24073994

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MEOX1 gene.

• not provided (72 variants)
• Inborn genetic diseases (9 variants)
• not specified (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MEOX1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	15	4	20
missense			40	5	2	47
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding			1	1	4	6
Total	0	0	43	21	10

Variants in MEOX1

This is a list of pathogenic ClinVar variants found in the MEOX1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-43641920-C-T			Uncertain significance (Aug 31, 2022)
17-43641935-G-A			Uncertain significance (Apr 05, 2023)
17-43641938-TC-T			Uncertain significance (Jun 22, 2022)
17-43641946-C-T			Likely benign (Aug 02, 2021)
17-43641948-C-T		Inborn genetic diseases	Uncertain significance (Jan 23, 2024)
17-43641949-A-C			Likely benign (Aug 30, 2023)
17-43641954-C-G		Inborn genetic diseases	Uncertain significance (Jan 16, 2024)
17-43641962-T-C		MEOX1-related disorder	Likely benign (Jan 19, 2024)
17-43641967-G-A			Likely benign (Dec 17, 2022)
17-43641975-G-T		MEOX1-related disorder	Likely benign (Dec 12, 2023)
17-43641985-C-T			Likely benign (Dec 12, 2023)
17-43641993-G-A		Inborn genetic diseases	Uncertain significance (Aug 04, 2023)
17-43641994-C-T			Likely benign (Oct 09, 2021)
17-43642010-C-T			Uncertain significance (Aug 24, 2023)
17-43642011-G-A		Klippel-Feil syndrome 2, autosomal recessive	Pathogenic (Jan 10, 2013)
17-43642012-G-A			Likely benign (Jul 19, 2023)
17-43642032-C-T		Inborn genetic diseases	Uncertain significance (Feb 28, 2024)
17-43642043-A-G			Likely benign (May 11, 2023)
17-43642252-G-A			Benign (Jun 20, 2021)
17-43643471-G-T			Likely benign (Jan 21, 2022)
17-43643477-C-T			Likely benign (Jan 15, 2024)
17-43643484-G-T			Benign (Jan 31, 2024)
17-43643494-C-T			Likely benign (Jul 02, 2022)
17-43643509-G-A			Uncertain significance (Mar 28, 2022)
17-43643516-G-A			Uncertain significance (Mar 28, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MEOX1	protein_coding	protein_coding	ENST00000318579	3	21567

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000191	0.730	125735	0	12	125747	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.261	155	146	1.06	0.00000866	1633
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000916	0.0000905
Ashkenazi Jewish	0.00	0.00
East Asian	0.000168	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000453	0.0000439
Middle Eastern	0.000168	0.000163
South Asian	0.0000337	0.0000327
Other	0.000164	0.000163

dbNSFP

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

Haploinsufficiency Scores

• pHI: 0.833
• hipred: N
• hipred_score: 0.230
• ghis: 0.421

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.970

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Meox1
• Phenotype: muscle phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; embryo phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Zebrafish Information Network

• Gene name: meox1
• Affected structure: xanthophore
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: somite specification;multicellular organism development;biological_process;positive regulation of transcription by RNA polymerase II;hematopoietic stem cell differentiation;somite development;sclerotome development
• Cellular component: nucleus;cytoplasm
• 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;protein binding;sequence-specific DNA binding;HMG box domain binding