HMX1

H6 family homeobox 1, the group of NKL subclass homeoboxes and pseudogenes

Basic information

Region (hg38): 4:8846076-8871839

Links

ENSG00000215612 ∙ NCBI:3166 ∙ OMIM:142992 ∙ HGNC:5017 ∙ Uniprot:Q9NP08 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• oculoauricular syndrome (Strong), mode of inheritance: AR
• oculoauricular syndrome (Strong), mode of inheritance: AR
• oculoauricular syndrome (Strong), mode of inheritance: AR
• oculoauricular syndrome (Supportive), mode of inheritance: AR
• oculoauricular syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Oculoauricular syndrome	AD	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	Craniofacial; Ophthalmologic	18423520; 21417677; 25574057

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HMX1 gene.

• Isolated microphthalmia 6 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HMX1 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	95	2	98
missense			188	2	5	195
nonsense			2			2
start loss			1			1
frameshift	1		4			5
inframe indel			10			10
splice donor/acceptor (+/-2bp)						0
splice region			1	1		2
non coding				11	8	19
Total	1	0	206	108	15

Variants in HMX1

This is a list of pathogenic ClinVar variants found in the HMX1 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-8846143-C-T		HMX1-related disorder	Likely benign (Jun 27, 2019)
4-8867402-G-GGCCCA			Benign (Jul 31, 2018)
4-8867531-A-G			Benign (Jun 29, 2018)
4-8867547-G-A			Benign (Jul 31, 2018)
4-8867621-C-G			Likely benign (Jan 16, 2019)
4-8867639-C-T			Benign (Jul 31, 2018)
4-8867691-G-A		HMX1-related disorder	Likely benign (Apr 17, 2019)
4-8867694-C-T			Likely benign (Jul 12, 2022)
4-8867710-T-C			Uncertain significance (Nov 24, 2020)
4-8867714-C-T			Likely benign (Oct 27, 2021)
4-8867716-C-T		Inborn genetic diseases	Uncertain significance (Dec 27, 2023)
4-8867719-G-A		Inborn genetic diseases	Uncertain significance (Apr 06, 2023)
4-8867726-G-A			Likely benign (Nov 18, 2023)
4-8867728-G-A			Uncertain significance (May 12, 2022)
4-8867739-G-A			Uncertain significance (Jun 23, 2020)
4-8867739-G-C		Inborn genetic diseases	Uncertain significance (Sep 14, 2022)
4-8867740-C-T		Inborn genetic diseases	Uncertain significance (Jun 29, 2023)
4-8867741-G-A			Likely benign (Mar 19, 2020)
4-8867745-G-T		Inborn genetic diseases	Uncertain significance (Sep 28, 2022)
4-8867747-G-A			Likely benign (Aug 04, 2023)
4-8867753-G-A			Likely benign (Jun 14, 2022)
4-8867754-G-A		Inborn genetic diseases	Uncertain significance (Nov 19, 2022)
4-8867757-A-G			Uncertain significance (Nov 18, 2021)
4-8867759-C-A		HMX1-related disorder	Likely benign (Apr 15, 2022)
4-8867759-C-G			Likely benign (Aug 10, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HMX1	protein_coding	protein_coding	ENST00000400677	2	25742

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.726	0.262	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.102	73	70.6	1.03	0.00000348	2057
Missense in Polyphen		18	24.658	0.72999		467
Synonymous	-0.460	36	32.7	1.10	0.00000175	816
Loss of Function	1.92	0	4.28	0.00	1.90e-7	87

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: DNA-binding protein that binds to the 5'-CAAG-3' core sequence. May function as a transcriptional repressor. Seems to act as a transcriptional antagonist of NKX2-5. May play an important role in the development of craniofacial structures such as the eye and ear. {ECO:0000269|PubMed:10206974}.
• Disease: DISEASE: Oculoauricular syndrome (OCACS) [MIM:612109]: A syndrome characterized by microphthalmia, microcornea, anterior segment dysgenesis, cataract, ocular coloboma, retinal pigment epithelium abnormalities, rod-cone dystrophy, and anomalies of the external ear. {ECO:0000269|PubMed:18423520}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Haploinsufficiency Scores

• pHI: 0.0957
• hipred: N
• hipred_score: 0.367
• ghis: 0.463

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.283

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hmx1
• Phenotype: skeleton 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); hearing/vestibular/ear phenotype; vision/eye 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); cellular phenotype; craniofacial phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: hmx1
• Affected structure: solid lens vesicle
• Phenotype tag: abnormal
• Phenotype quality: decreased occurrence

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;multicellular organism development;negative regulation of transcription, DNA-templated
• Cellular component: nucleus
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA binding