ZYG11B

protein-coding

zyg-11 family member B, cell cycle regulator, the group of ZYG11 cell cycle regulator family|Armadillo like helical domain containing

Gene summary

Involved in positive regulation of proteasomal ubiquitin-dependent protein catabolic process and protein quality control for misfolded or incompletely synthesized proteins. Part of Cul2-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

ZYG11

MANE transcript

NM_024646.3

Inheritance

AR, AD

ClinVar variants

P:1U:69

Top phenotype

ZYG11B-related disorder

gnomAD constraint

pLI —, LoF o/e 0.11

Max pathogenic AF

—

Genomic locus

chr1:52,726,453-52,827,336

External References & Databases

Ensembl (ENSG00000162378)

Transcript & Mutation Effects

hg38 • Region Span ~100.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

multiple congenital anomalies/dysmorphic syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0019042

Submitter: LiferaOmics

Genetic evidence – Published (AR scope) No scorable published cases of biallelic (autosomal recessive) ZYG11B variants causing oculo-auriculo-vertebral spectrum were identified. Published genetic evidence total = 0 / 12 Published (AD context; not scored for AR) ZYG11B-related oculo-auriculo-vertebral spectrum has been reported in an autosomal dominant (de novo heterozygous) context (PMID: 32738032). This evidence is not scorable under the autosomal recessive model. AD-context evidence total (not scored for AR) = 0 Genetic evidence – Our case Family 1 – one proband. Case-level (AR homozygous; predicted null frameshift; AR predicted null default = 1.5; consanguineous family → −0.5 applied) = 1.0; Segregation = 0; Case-control = 0 Family 1 total = 1.0 Total genetic evidence (Published AR + Our case) 1.0 / 12 Experimental evidence – Published (biological plausibility only; conservative) ZYG11B has been shown to play a role in craniofacial and axial development. Zebrafish knockdown models demonstrate craniofacial and vertebral abnormalities, supporting biological plausibility for involvement in oculo-auriculo-vertebral spectrum. Model system (gene role in craniofacial development; biological plausibility only) = 0.5 Experimental evidence total = 0.5 / 6 Overall score Genetic evidence = 1.0 Experimental evidence = 0.5 Total = 1.5

multiple congenital anomalies/dysmorphic syndromeLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0019042

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZYG11B variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 54

not providedTotal: 2

ZYG11B-related disorderTotal: 1

Craniofacial microsomia 1Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024646.3. 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			2 clinvar			2
missense			56 clinvar			56
nonsense		1 clinvar	2 clinvar			3
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	1	69	0	0	70

Highest pathogenic variant AF is 0.0000013686443

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024646.3	RefSeq	NP_078922.1	14	MANE Select
ENST00000294353.7	Ensembl	ENSP00000294353.6	14	MANE Select
NM_001441954.1	RefSeq	NP_001428883.1	14	Standard
ENST00000545132.5	Ensembl	ENSP00000441315.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein ubiquitination

Cellular Component

Cul2-RING ubiquitin ligase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000294353
Coding exons: 14
Length: 100889
Individuals with no LoFs: 125724
Homozygous LoFs: 1
Heterozygous LoFs: 20
Defined: 125745
p: 0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.98	176	400	0.440	0.0000207	4902
Missense (PolyPhen)		27	76.35	0.35363		970
Synonymous	-0.971	156	141	1.10	0.00000685	1439
Loss of Function	4.97	4	36.3	0.110	0.00000193	419

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00014	0.00012	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.00011	0.000099	rare
East Asian	0.000055	0.000054	rare
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.000079	0.000070	rare
South Asian	0	0.0	absent
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probably acts as target recruitment subunit in the E3 ubiquitin ligase complex ZYG11B-CUL2-Elongin BC.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.362
RVIS EVS: -1
RVIS percentile EVS: 8.32

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.662

Gene Damage Prediction

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