NBAS

protein-coding

NBAS subunit of NRZ tethering complex, the group of NRZ tethering complex

Gene summary

This gene encodes a protein with two leucine zipper domains, a ribosomal protein S14 signature domain and a Sec39 like domain. The protein is thought to be involved in Golgi-to-ER transport. Mutations in this gene are associated with short stature, optic nerve atrophy, and Pelger-Huet anomaly. [provided by RefSeq, Oct 2012]

MANE transcript

NM_015909.4

Inheritance

ClinVar variants

P:273U:979B:936

Top phenotype

Infantile liver failure syndrome 2; Short stature, optic nerve atrophy, and Pelger-Huet anomaly (SOPH syndrome)

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr2:15,166,916-15,561,340

External References & Databases

Ensembl (ENSG00000151779)

Transcript & Mutation Effects

hg38 • Region Span ~394.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

infantile liver failure syndrome 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014659

Submitter: Labcorp Genetics (formerly Invitae)

infantile liver failure syndrome 2SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014659

Submitter: Orphanet

short stature-optic atrophy-Pelger-Huët anomaly syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013889

Submitter: Orphanet

hereditary hemophagocytic lymphohistiocytosisSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0015541

Submitter: PanelApp Australia

short stature-optic atrophy-Pelger-Huët anomaly syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013889

Submitter: Labcorp Genetics (formerly Invitae)

short stature-optic atrophy-Pelger-Huët anomaly syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013889

Submitter: PanelApp Australia

short stature-optic atrophy-Pelger-Huët anomaly syndromeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013889

Submitter: Illumina

short stature-optic atrophy-Pelger-Huët anomaly syndromeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013889

Submitter: G2P

Clinical Genomic Database (CGD)

Infantile liver failure syndrome 2; Short stature, optic nerve atrophy, and Pelger-Huet anomaly (SOPH syndrome)AR

Manifestation: Craniofacial; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Ophthalmologic

Intervention: General

Rationale: 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

Refs: 20577004; 26073778

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NBAS variants in ClinVar

22 Conditions Cataloged

not providedTotal: 2513

Inborn genetic diseasesTotal: 406

NBAS-related disorderTotal: 209

not specifiedTotal: 169

Infantile liver failure syndrome 2Total: 119

Short stature-optic atrophy-Pelger-Huët anomaly syndromeTotal: 98

Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteinsTotal: 28

Retinal dystrophyTotal: 12

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015909.4. 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	1 clinvar	14 clinvar	654 clinvar	8 clinvar	678
missense	2 clinvar	22 clinvar	960 clinvar	265 clinvar	9 clinvar	1258
nonsense	55 clinvar	32 clinvar	1 clinvar			88
start loss		2 clinvar				2
frameshift	60 clinvar	36 clinvar	1 clinvar			97
splice donor/acceptor (+/-2bp)	2 clinvar	60 clinvar	3 clinvar			65
Total	120	153	979	919	17	2188

Highest pathogenic variant AF is 0.00025660224

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015909.4	RefSeq	NP_056993.2	52	MANE Select
ENST00000281513.10	Ensembl	ENSP00000281513.5	52	MANE Select
ENST00000423602.1	Ensembl	ENSP00000403119.1	4	Standard
ENST00000427792.1	Ensembl	ENSP00000402458.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
nbas	Danio rerio	Structure: somite Quality: malformed abnormal

Gene / Model

Organism

Observed Phenotype

nbas

Danio rerio

Structure: somite

Quality: malformed

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Vesicle-mediated transport
Membrane Trafficking
COPI-dependent Golgi-to-ER retrograde traffic
Golgi-to-ER retrograde transport
Intra-Golgi and retrograde Golgi-to-ER traffic

Biological Process

nuclear-transcribed mRNA catabolic process
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum
protein transport
negative regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay

Molecular Function

SNARE binding

Cellular Component

endoplasmic reticulum
endoplasmic reticulum membrane
cytosol
membrane
Dsl1/NZR complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000281513
Coding exons: 52
Length: 394423
Individuals with no LoFs: 125350
Homozygous LoFs: 0
Heterozygous LoFs: 398
Defined: 125748
p: 0.00158

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.875	1342	1.25e+3	1.07	0.0000677	15446
Missense (PolyPhen)		332	341.23	0.97295		4105
Synonymous	-3.17	552	465	1.19	0.0000252	4532
Loss of Function	3.79	90	138	0.652	0.00000742	1634

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0015	0.0015	notable
Latino/Admixed American	0.0021	0.0021	notable
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00093	0.00092	rare
Finnish	0.0015	0.0015	notable
European (Non-Finnish)	0.0018	0.0018	notable
South Asian	0.00075	0.00075	rare
Other	0.0031	0.0031	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in Golgi-to-endoplasmic reticulum (ER) retrograde transport; the function is proposed to depend on its association in the NRZ complex which is believed to play a role in SNARE assembly at the ER (PubMed:19369418). {ECO:0000269|PubMed:19369418, ECO:0000305}.;
Disease: DISEASE: Infantile liver failure syndrome 2 (ILFS2) [MIM:616483]: A form of infantile liver failure syndrome, a life-threatening disorder of hepatic function that manifests with acute liver failure in the first few months of life. Clinical features include anemia, renal tubulopathy, developmental delay, seizures, failure to thrive, and liver steatosis and fibrosis. {ECO:0000269|PubMed:26073778}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=NBAS mutations have been found in a multisystem disease affecting the liver, eye, immune system, connective tissue, and bone. Clinical manifestations include a progeroid appearance, short stature, slender bones, epiphyseal dysplasia with multiple phalangeal pseudo-epiphyses, cervical instability, myelopathy, elevated transaminases, hypogammaglobulinemia, reduced natural killer cells, Pelger-Huet anomaly of granulocytes, and in some cases retinal dystrophy and optic atrophy. {ECO:0000269|PubMed:26286438}.;

Intolerance Scores

LoFtool: 0.944
RVIS EVS: -0.22
RVIS percentile EVS: 37.33

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: N
Indispensability score: 0.0491

Gene Damage Prediction

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