SHOX2

short stature homeobox 2, the group of PRD class homeoboxes and pseudogenes

Basic information

Region (hg38): 3:158095905-158106420

Links

ENSG00000168779 ∙ NCBI:6474 ∙ OMIM:602504 ∙ HGNC:10854 ∙ Uniprot:O60902 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• schizophrenia (No Known Disease Relationship), mode of inheritance: Unknown

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SHOX2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SHOX2 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			2	5	1	8
missense			27	2		29
nonsense						0
start loss						0
frameshift						0
inframe indel				1		1
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	29	8	1

Variants in SHOX2

This is a list of pathogenic ClinVar variants found in the SHOX2 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-158098110-C-A		not specified	Uncertain significance (Dec 12, 2023)
3-158098130-G-C		not specified	Uncertain significance (Feb 15, 2023)
3-158098135-G-C			Likely benign (Mar 01, 2023)
3-158098148-T-C		not specified	Uncertain significance (Apr 08, 2023)
3-158098196-A-G		not specified	Uncertain significance (Dec 15, 2023)
3-158098211-T-C		not specified	Uncertain significance (Jun 27, 2022)
3-158098221-G-C		not specified	Uncertain significance (Apr 18, 2023)
3-158098227-G-T		not specified	Uncertain significance (Jun 26, 2023)
3-158098230-G-A		not specified	Uncertain significance (Nov 17, 2022)
3-158098308-T-G		not specified	Uncertain significance (Apr 12, 2024)
3-158099931-C-T		not specified	Uncertain significance (Dec 19, 2023)
3-158099932-G-A			Benign (Dec 13, 2018)
3-158099940-T-G		not specified	Uncertain significance (Dec 28, 2022)
3-158100311-C-T		not specified	Uncertain significance (Mar 24, 2023)
3-158100317-G-C		SHOX2-related disorder	Likely benign (Oct 04, 2019)
3-158102696-C-A		SHOX2-related disorder	Likely benign (Apr 01, 2019)
3-158102837-G-C		not specified	Uncertain significance (Apr 29, 2024)
3-158102878-C-T		not specified	Uncertain significance (Aug 08, 2023)
3-158105069-A-C		not specified	Uncertain significance (Jul 13, 2022)
3-158105089-C-T			Uncertain significance (Jan 28, 2015)
3-158105682-C-T		not specified	Uncertain significance (Mar 31, 2022)
3-158105714-C-G		not specified	Uncertain significance (Feb 15, 2023)
3-158105719-G-C		SHOX2-related disorder	Likely benign (Apr 08, 2019)
3-158105721-C-T			Uncertain significance (Jan 01, 2020)
3-158105730-T-A			Uncertain significance (Aug 21, 2015)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SHOX2	protein_coding	protein_coding	ENST00000389589	6	9345

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0161	0.962	125741	0	6	125747	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0998	196	192	1.02	0.00000879	2243
Missense in Polyphen		72	92.733	0.77642		1106
Synonymous	-1.38	104	87.6	1.19	0.00000430	758
Loss of Function	1.99	5	12.7	0.395	5.67e-7	159

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000128	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000183	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.0000328	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be a growth regulator and have a role in specifying neural systems involved in processing somatosensory information, as well as in face and body structure formation.

Recessive Scores

• pRec: 0.130

Intolerance Scores

• loftool: 0.127
• rvis_EVS: -0.41
• rvis_percentile_EVS: 26.23

Haploinsufficiency Scores

• pHI: 0.831
• hipred: Y
• hipred_score: 0.711
• ghis: 0.575

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.955

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Shox2
• Phenotype: craniofacial phenotype; homeostasis/metabolism 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); 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); growth/size/body region 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); limbs/digits/tail phenotype; digestive/alimentary phenotype; skeleton phenotype

Zebrafish Information Network

• Gene name: shox2
• Affected structure: sinus venosus
• Phenotype tag: abnormal
• Phenotype quality: hypoplastic

Gene ontology

• Biological process: skeletal system development;osteoblast differentiation;positive regulation of mesenchymal cell proliferation;chondrocyte development;heart valve development;cardiac atrium morphogenesis;regulation of transcription by RNA polymerase II;nervous system development;heart development;regulation of chondrocyte differentiation;embryonic forelimb morphogenesis;positive regulation of smoothened signaling pathway;embryonic digestive tract morphogenesis;positive regulation of skeletal muscle fiber development;positive regulation of axonogenesis;embryonic skeletal joint morphogenesis;cartilage development involved in endochondral bone morphogenesis;muscle tissue morphogenesis;regulation of branching morphogenesis of a nerve
• Cellular component: nucleus
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;sequence-specific DNA binding