IRX5

iroquois homeobox 5, the group of TALE class homeoboxes and pseudogenes

Basic information

Region (hg38): 16:54930865-54934485

Links

ENSG00000176842 ∙ NCBI:10265 ∙ OMIM:606195 ∙ HGNC:14361 ∙ Uniprot:P78411 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• craniofacial dysplasia - osteopenia syndrome (Strong), mode of inheritance: AR
• craniofacial dysplasia - osteopenia syndrome (Limited), mode of inheritance: AR
• craniofacial dysplasia - osteopenia syndrome (Supportive), mode of inheritance: AR
• craniofacial dysplasia - osteopenia syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hamamy syndrome	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	Craniofacial; Dental; Musculoskeletal; Neurologic; Ophthalmologic	17230486; 22581230; 34899143

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IRX5 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IRX5 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				29	2	31
missense			53	2	2	57
nonsense						0
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					4	4
Total	0	0	54	31	8

Variants in IRX5

This is a list of pathogenic ClinVar variants found in the IRX5 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-54930964-A-G			Benign (Nov 12, 2018)
16-54931220-T-C		IRX5-related disorder	Likely benign (Oct 28, 2019)
16-54931254-C-T		Inborn genetic diseases	Uncertain significance (Feb 22, 2023)
16-54931311-G-T		Inborn genetic diseases	Uncertain significance (Jan 03, 2024)
16-54931360-C-T			Likely benign (Aug 16, 2022)
16-54931374-C-A		Inborn genetic diseases	Uncertain significance (Feb 10, 2022)
16-54931398-A-G		Inborn genetic diseases	Uncertain significance (Oct 26, 2021)
16-54931400-G-A		Inborn genetic diseases	Uncertain significance (Jun 10, 2022)
16-54931402-C-A			Likely benign (Apr 26, 2023)
16-54931417-C-T		IRX5-related disorder	Likely benign (Apr 30, 2019)
16-54931434-TCTC-T		Craniofacial dysplasia - osteopenia syndrome • Inborn genetic diseases	Uncertain significance (Jun 03, 2022)
16-54931629-C-G			Benign (Nov 12, 2018)
16-54932505-C-T		Inborn genetic diseases	Uncertain significance (Feb 27, 2023)
16-54932509-C-T			Likely benign (Sep 06, 2022)
16-54932513-C-A		Inborn genetic diseases	Uncertain significance (Aug 14, 2023)
16-54932518-A-T			Likely benign (Apr 30, 2018)
16-54932605-C-T			Likely benign (Aug 21, 2023)
16-54932629-C-T			Likely benign (Jun 22, 2018)
16-54932636-G-A		Inborn genetic diseases	Uncertain significance (Jan 10, 2023)
16-54932647-C-G		Inborn genetic diseases	Uncertain significance (Dec 07, 2021)
16-54932668-C-T			Likely benign (Dec 07, 2023)
16-54932686-G-A			Likely benign (Dec 31, 2019)
16-54932696-G-C		Craniofacial dysplasia - osteopenia syndrome	Pathogenic (May 13, 2012)
16-54932746-C-A		Craniofacial dysplasia - osteopenia syndrome	Pathogenic (May 13, 2012)
16-54932749-G-A			Likely benign (Sep 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IRX5	protein_coding	protein_coding	ENST00000394636	3	3624

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.975	0.0253	125288	0	5	125293	0.0000200

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.831	232	270	0.858	0.0000129	3015
Missense in Polyphen		38	67.619	0.56197		741
Synonymous	-1.42	149	129	1.16	0.00000657	1057
Loss of Function	3.44	1	15.7	0.0636	7.29e-7	179

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000296	0.0000296
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000555	0.0000547
Finnish	0.00	0.00
European (Non-Finnish)	0.0000266	0.0000265
Middle Eastern	0.0000555	0.0000547
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Establishes the cardiac repolarization gradient by its repressive actions on the KCND2 potassium-channel gene. Required for retinal cone bipolar cell differentiation. May regulate contrast adaptation in the retina and control specific aspects of visual function in circuits of the mammalian retina (By similarity). Could be involved in the regulation of both the cell cycle and apoptosis in prostate cancer cells. Involved in craniofacial and gonadal development. Modulates the migration of progenitor cell populations in branchial arches and gonads by repressing CXCL12. {ECO:0000250, ECO:0000269|PubMed:22581230}.
• Disease: DISEASE: Hamamy syndrome (HMMS) [MIM:611174]: A syndrome characterized by severe hypertelorism, upslanting palpebral fissures, brachycephaly, abnormal ears, sloping shoulders, enamel hypoplasia, and osteopenia with repeated fractures. Additional features include myopia, mild to moderate sensorineural hearing loss, gonadal anomalies and borderline intelligence. {ECO:0000269|PubMed:22581230}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: FTO Obesity Variant Mechanism;Preimplantation Embryo (Consensus)

Recessive Scores

• pRec: 0.130

Haploinsufficiency Scores

• pHI: 0.664
• ghis: 0.443

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.508

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Irx5
• Phenotype: growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); vision/eye 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)

Gene ontology

• Biological process: regulation of heart rate;regulation of transcription by RNA polymerase II;visual perception;gonad development;neuron maturation;embryonic cranial skeleton morphogenesis;response to stimulus;retinal bipolar neuron differentiation
• Cellular component: nucleus
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;vitamin D binding;sequence-specific DNA binding