SMC4

protein-coding

structural maintenance of chromosomes 4, the group of Structural maintenance of chromosomes proteins|Condensin I subunits|Condensin II subunits|MicroRNA protein coding host genes

Gene summary

This gene belongs to the 'structural maintenance of chromosomes' (SMC) gene family. Members of this gene family play a role in two changes in chromosome structure during mitotic segregation of chromosomes- chromosome condensation and sister chromatid cohesion. The protein encoded by this gene is likely a subunit of the 13S condensin complex, which is involved in chromosome condensation. A pseudogene related to this gene is located on chromosome 2. [provided by RefSeq, Jun 2016]

Previous symbols:

SMC4L1

MANE transcript

NM_001002800.3

Inheritance

—

ClinVar variants

U:165B:6

Top phenotype

Bone marrow failure syndrome

gnomAD constraint

pLI —, LoF o/e 0.33

Max pathogenic AF

—

Genomic locus

chr3:160,399,274-160,434,954

External References & Databases

Ensembl (ENSG00000113810)

Transcript & Mutation Effects

hg38 • Region Span ~35.7 kb

Loading mutation effect viewer...

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 SMC4 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 154

not providedTotal: 5

Bone marrow failure syndromeTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001002800.3. 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			3 clinvar	1 clinvar		4
missense			158 clinvar	4 clinvar	1 clinvar	163
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	165	5	1	171

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_001002800.3	RefSeq	NP_001002800.1	23	MANE Select
ENST00000357388.8	Ensembl	ENSP00000349961.3	23	MANE Select
NM_001288753.2	RefSeq	NP_001275682.1	23	Standard
NM_005496.3	RefSeq	NP_005487.3	23	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
smc4	Danio rerio	Structure: head Quality: decreased size abnormal

Gene / Model

Organism

Observed Phenotype

smc4

Danio rerio

Structure: head

Quality: decreased size

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Condensation of Prophase Chromosomes
Mitotic Prophase
Condensation of Prometaphase Chromosomes
Mitotic Prometaphase
M Phase

Biological Process

mitotic sister chromatid segregation
mitotic chromosome condensation
meiotic chromosome condensation
meiotic chromosome segregation
cell division

Molecular Function

single-stranded DNA binding
protein binding
ATP binding
protein heterodimerization activity

Cellular Component

condensin complex
nucleus
nucleoplasm
cytosol
nuclear speck

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000357388
Coding exons: 23
Length: 35689
Individuals with no LoFs: 125600
Homozygous LoFs: 0
Heterozygous LoFs: 147
Defined: 125747
p: 0.000585

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.08	574	652	0.881	0.0000332	8566
Missense (PolyPhen)		109	163.93	0.66492		2116
Synonymous	-1.60	248	218	1.14	0.0000114	2257
Loss of Function	4.81	20	60.3	0.331	0.00000297	853

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00065	0.00055	rare
Latino/Admixed American	0.00052	0.00049	rare
Ashkenazi Jewish	0.00094	0.00079	rare
East Asian	0.0014	0.0013	notable
Finnish	0.00024	0.00018	rare
European (Non-Finnish)	0.00059	0.00054	rare
South Asian	0.00086	0.00078	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Central component of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases. {ECO:0000269|PubMed:11136719}.;

Recessive Scores

pRec: 0.276

Intolerance Scores

LoFtool: 0.385
RVIS EVS: -0.99
RVIS percentile EVS: 8.6

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.893

Gene Damage Prediction

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