SHB

protein-coding

SH2 domain containing adaptor protein B, the group of SH2 domain containing

Gene summary

Enables phosphotyrosine residue binding activity. Predicted to be involved in signal transduction. Predicted to act upstream of or within several processes, including hematopoietic stem cell proliferation; negative regulation of oocyte maturation; and positive regulation of immune response. Located in cytosol. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_003028.3

Inheritance

—

ClinVar variants

U:115B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr9:37,915,898-38,069,227

External References & Databases

Ensembl (ENSG00000107338)

Transcript & Mutation Effects

hg38 • Region Span ~153.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SHB variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 115

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003028.3. 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	2 clinvar	3 clinvar	6
missense			112 clinvar	2 clinvar		114
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	115	4	3	122

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003028.3	RefSeq	NP_003019.2	6	MANE Select
ENST00000377707.4	Ensembl	ENSP00000366936.3	6	MANE Select
ENST00000854896.1	Ensembl	ENSP00000524955.1	5	Standard
ENST00000854896.2	Ensembl	ENSP00000524955.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Angiogenesis overview
VEGFA-VEGFR2 Signaling Pathway
Signal Transduction
VEGFA-VEGFR2 Pathway
TCR

Biological Process

angiogenesis
apoptotic process
signal transduction
positive regulation of signal transduction
cell differentiation

Molecular Function

phosphotyrosine residue binding
SH3/SH2 adaptor activity
protein binding

Cellular Component

nucleoplasm
cytosol
plasma membrane
cytoplasmic ribonucleoprotein granule

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000377707
Coding exons: 6
Length: 150080
Individuals with no LoFs: 124814
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 124817
p: 0.0000120

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.241	246	257	0.958	0.0000148	3164
Missense (PolyPhen)		57	81.636	0.69822		927
Synonymous	0.447	102	108	0.945	0.00000667	991
Loss of Function	3.68	2	19.6	0.102	9.21e-7	241

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Adapter protein which regulates several signal transduction cascades by linking activated receptors to downstream signaling components. May play a role in angiogenesis by regulating FGFR1, VEGFR2 and PDGFR signaling. May also play a role in T-cell antigen receptor/TCR signaling, interleukin-2 signaling, apoptosis and neuronal cells differentiation by mediating basic- FGF and NGF-induced signaling cascades. May also regulate IRS1 and IRS2 signaling in insulin-producing cells. {ECO:0000269|PubMed:10828022, ECO:0000269|PubMed:10837138, ECO:0000269|PubMed:12084069, ECO:0000269|PubMed:12464388, ECO:0000269|PubMed:12520086, ECO:0000269|PubMed:15026417, ECO:0000269|PubMed:15919073, ECO:0000269|PubMed:8806685, ECO:0000269|PubMed:9484780, ECO:0000269|PubMed:9751119}.;

Recessive Scores

pRec: 0.121

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.655

Gene Damage Prediction

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