SMC1B

Summary

SMC1B (structural maintenance of chromosomes 1B, HGNC:11112) is a protein-coding gene on chromosome 22q13.31, encoding Structural maintenance of chromosomes protein 1B (Q8NDV3). Meiosis-specific component of cohesin complex.

SMC1L2 belongs to a family of proteins required for chromatid cohesion and DNA recombination during meiosis and mitosis (3:Revenkova et al., 2001 [PubMed 11564881]).

Source: NCBI Gene 27127 — RefSeq curated summary.

At a glance

• Gene–disease (curated): gonadal dysgenesis (Limited, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 166 total — 1 likely-pathogenic
• MANE Select transcript: NM_148674

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11112
Approved symbol	SMC1B
Name	structural maintenance of chromosomes 1B
Location	22q13.31
Locus type	gene with protein product
Status	Approved
Aliases	bK268H5
Ensembl gene	ENSG00000077935
Ensembl biotype	protein_coding
OMIM	608685
Entrez	27127

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000357450, ENST00000404354, ENST00000877413, ENST00000923332

RefSeq mRNA: 2 — MANE Select: NM_148674 NM_001291501, NM_148674

CCDS: CCDS43027, CCDS74876

Canonical transcript exons

ENST00000357450 — 25 exons

Exon	Start	End
ENSE00000507372	45399095	45399353
ENSE00000507375	45393634	45393841
ENSE00000657085	45383467	45383613
ENSE00000657086	45386867	45387046
ENSE00000657087	45389712	45389897
ENSE00000657093	45406460	45406663
ENSE00000657095	45408710	45408898
ENSE00000880733	45372155	45372292
ENSE00000880734	45394685	45394767
ENSE00000880735	45396346	45396486
ENSE00000880736	45402333	45402571
ENSE00001046470	45345459	45345569
ENSE00001046490	45349728	45349797
ENSE00001107573	45352451	45352602
ENSE00001107583	45353978	45354132
ENSE00001274454	45358697	45358795
ENSE00001340317	45354959	45355115
ENSE00001340453	45359805	45359958
ENSE00001340460	45406753	45406865
ENSE00001404707	45371471	45371587
ENSE00001405948	45369954	45370060
ENSE00001406353	45362885	45363026
ENSE00001406994	45361839	45361984
ENSE00001548476	45344063	45344657
ENSE00001907828	45413459	45413599

Expression profiles

Bgee: expression breadth broad, 31 present calls, max score 91.27.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4520 / max 68.1589, expressed in 116 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194576	0.3693	92
194577	0.0562	22
194578	0.0266	10

Top tissues by expression

175 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.27	gold quality
right testis	UBERON:0004534	88.90	gold quality
left testis	UBERON:0004533	87.32	gold quality
testis	UBERON:0000473	85.45	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.48	gold quality
buccal mucosa cell	CL:0002336	68.50	silver quality
tendon of biceps brachii	UBERON:0008188	52.73	gold quality
colonic epithelium	UBERON:0000397	52.00	silver quality
bone marrow cell	CL:0002092	51.99	gold quality
monocyte	CL:0000576	51.52	silver quality
leukocyte	CL:0000738	51.38	silver quality
calcaneal tendon	UBERON:0003701	49.65	silver quality
lymph node	UBERON:0000029	49.44	gold quality
tonsil	UBERON:0002372	47.40	gold quality
vermiform appendix	UBERON:0001154	45.39	gold quality
gall bladder	UBERON:0002110	44.99	silver quality
hindlimb stylopod muscle	UBERON:0004252	44.89	gold quality
granulocyte	CL:0000094	44.88	silver quality
caecum	UBERON:0001153	44.09	silver quality
vastus lateralis	UBERON:0001379	44.00	gold quality
quadriceps femoris	UBERON:0001377	43.90	gold quality
cortical plate	UBERON:0005343	43.43	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
ventricular zone	UBERON:0003053	43.31	gold quality
skeletal muscle tissue	UBERON:0001134	42.98	gold quality
blood	UBERON:0000178	42.92	gold quality
adult organism	UBERON:0007023	42.66	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
oviduct epithelium	UBERON:0004804	41.49	gold quality
sural nerve	UBERON:0015488	41.46	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-124263	yes	2420.81
E-ANND-3	yes	5.88

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F6

miRNA regulators (miRDB)

40 targeting SMC1B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-146A-3P	99.13	68.99	1881
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-4724-5P	98.87	67.75	1324

Literature-anchored findings (GeneRIF, showing 3)

• High SMC1B expression is associated with pancreatic cancer. (PMID:25216700)
• Data show that structural maintenance of chromosomes protein 1B (SMC1B) is expressed in primary fibroblasts. (PMID:26673124)
• Through the translational regulation of novel RNA targets SMC1B and TEX11, DAZL may have a key role in regulating chromosome cohesion and DNA recombination; two processes fundamental in determining oocyte quality and whose establishment in foetal life may support lifelong fertility. (PMID:28364521)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	smc1b	ENSDARG00000014402
mus_musculus	Smc1b	ENSMUSG00000022432
rattus_norvegicus	Smc1b	ENSRNOG00000032570
drosophila_melanogaster	SMC3	FBGN0015615
caenorhabditis_elegans		WBGENE00004873
caenorhabditis_elegans		WBGENE00012198
caenorhabditis_elegans		WBGENE00019087

Paralogs (7): SMC1A (ENSG00000072501), SMC3 (ENSG00000108055), SMC4 (ENSG00000113810), CKAP4 (ENSG00000136026), SMC2 (ENSG00000136824), CCDC122 (ENSG00000151773), CCDC157 (ENSG00000187860)

Protein

Protein identifiers

Structural maintenance of chromosomes protein 1B — Q8NDV3 (reviewed: Q8NDV3)

All UniProt accessions (1): Q8NDV3

UniProt curated annotations — full annotation on UniProt →

Function. Meiosis-specific component of cohesin complex. Required for the maintenance of meiotic cohesion, but not, or only to a minor extent, for its establishment. Contributes to axial element (AE) formation and the organization of chromatin loops along the AE. Plays a key role in synapsis, recombination and chromosome movements. The cohesin complex is required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The meiosis-specific cohesin complex probably replaces mitosis specific cohesin complex when it dissociates from chromatin during prophase I.

Subunit / interactions. Forms a heterodimer with SMC3. Component of a meiosis-specific cohesin complex, probably composed of the SMC1B and SMC3 heterodimer attached via their SMC hinge domain, RAD21 (or its meiosis-specific related protein REC8), which link them, and STAG3, which interacts with RAD21 or REC8. The cohesin complex interacts with the cohesin loading complex subunits NIPBL/Scc2 (via HEAT repeats) and MAU2/Scc4. NIPBL directly contacts all members of the complex, RAD21, SMC1A/B, SMC3 and STAG1.

Subcellular location. Nucleus. Chromosome. Centromere.

Domain organisation. The flexible SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterotypic interaction with the corresponding domain of SMC3, forming a V-shaped heterodimer. The two heads of the heterodimer are then connected by different ends of the cleavable RAD21 or REC8 protein, forming a ring structure.

Similarity. Belongs to the SMC family. SMC1 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NDV3-3	1	yes
Q8NDV3-2	2

RefSeq proteins (2): NP_001278430, NP_683515* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003395	RecF/RecN/SMC_N	Domain
IPR010935	SMC_hinge	Domain
IPR024704	SMC	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR028468	Smc1_ABC	Domain
IPR036277	SMC_hinge_sf	Homologous_superfamily

Pfam: PF02463, PF06470

UniProt features (19 total): sequence variant 4, sequence conflict 4, coiled-coil region 4, modified residue 3, chain 1, domain 1, splice variant 1, binding site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NDV3-F1	83.44	0.20

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 32–39

Post-translational modifications (3): 648, 713, 1033

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1221632	Meiotic synapsis
R-HSA-1474165	Reproduction
R-HSA-1500620	Meiosis
R-HSA-1640170	Cell Cycle

MSigDB gene sets: 90 (showing top): GOBP_CHROMOSOME_ORGANIZATION, REACTOME_MEIOTIC_SYNAPSIS, KAUFFMANN_DNA_REPAIR_GENES, CAGCTG_AP4_Q5, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM5, GOBP_SISTER_CHROMATID_COHESION, FREDERICK_PRKCI_TARGETS, GATA4_Q3, KEGG_OOCYTE_MEIOSIS, GOBP_MEIOTIC_CELL_CYCLE, GOCC_CHROMOSOMAL_REGION, chr22q13, RFX1_01, GOCC_LATERAL_ELEMENT, GOCC_COHESIN_COMPLEX

GO Biological Process (3): sister chromatid cohesion (GO:0007062), meiotic cell cycle (GO:0051321), chromosome organization (GO:0051276)

GO Molecular Function (5): DNA binding (GO:0003677), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (10): chromosome, centromeric region (GO:0000775), lateral element (GO:0000800), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), meiotic cohesin complex (GO:0030893), condensed nuclear chromosome (GO:0000794), synaptonemal complex (GO:0000795), chromosome (GO:0005694), cohesin complex (GO:0008278)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Meiosis	1
Reproduction	1
Cell Cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cell cycle process	1
chromosome organization	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
organelle organization	1
nucleic acid binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
chromosomal region	1
synaptonemal complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
cohesin complex	1
nuclear chromosome	1
condensed chromosome	1
nucleus	1
synaptonemal structure	1
intracellular membraneless organelle	1
chromosome	1
protein-containing complex	1

Protein interactions and networks

STRING

2943 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMC1B	STAG3	Q9UJ98	998
SMC1B	REC8	O95072	996
SMC1B	RAD21L1	Q9H4I0	995
SMC1B	SMC3	Q9UQE7	993
SMC1B	RAD21	O60216	990
SMC1B	STAG1	Q8WVM7	875
SMC1B	STAG2	Q8N3U4	823
SMC1B	SYCP3	Q8IZU3	746
SMC1B	PDS5B	Q9NTI5	741
SMC1B	SPO11	Q9Y5K1	736
SMC1B	SYCP1	Q15431	714
SMC1B	HORMAD1	Q86X24	711
SMC1B	ESPL1	Q14674	678
SMC1B	PDS5A	Q29RF7	655
SMC1B	CDCA5	Q96FF9	653

IntAct

4 interactions, top by confidence:

A	B	Type	Score
RAD21	SMC1A	psi-mi:“MI:0914”(association)	0.930
SMC1B	SLTM	psi-mi:“MI:0915”(physical association)	0.400
SMC1B	H2BC21	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (15): SMC1B (Affinity Capture-MS), RAD21 (Co-fractionation), SMC1B (Co-fractionation), SMC1B (Co-fractionation), SMC3 (Co-fractionation), SMC1B (Affinity Capture-Western), SMC1B (Affinity Capture-Western), SMC1B (Affinity Capture-MS), SMC1B (Affinity Capture-MS), SMC1B (Proximity Label-MS), SLTM (Proximity Label-MS), SMC1B (Affinity Capture-MS), SMC1B (Affinity Capture-MS), SMC1B (Affinity Capture-MS), SMC1B (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: B2FDA8, G0SHW7, G5EG17, J9VL63, O01789, O13710, O42649, O93309, O94383, O95347, O97594, P32908, P38989, P41003, P41004, P47037, P48996, P50533, P53692, P92199, P97690, Q00737, Q08204, Q09591, Q12267, Q12749, Q18237, Q20060, Q54I56, Q54LV0, Q54PK4, Q552D9, Q5R4K5, Q6C3V4, Q6DRJ7, Q6P9I7, Q6Q1P4, Q802R8, Q8CG48, Q8NDV3

Diamond homologs: A3PMS2, A9II65, B8CW13, B8GZ28, B9E1H0, C4ZJU1, D4GUK1, E1X022, O66878, O95347, P15016, P32908, P41508, P47540, P48996, P50532, P50533, P75361, Q12267, Q1INB1, Q20060, Q24U48, Q54PK4, Q59037, Q5H054, Q5N0D2, Q604U6, Q69GZ5, Q6N1B7, Q6Q1P4, Q7NG51, Q7ZAK1, Q81ZL2, Q8CG47, Q8CG48, Q8KBS6, Q8NDV3, Q8REH4, Q8TZY2, Q90988

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

166 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	132
Likely benign	10
Benign	6

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1256022	NM_148674.5(SMC1B):c.863A>G (p.Glu288Gly)	Likely pathogenic

SpliceAI

4050 predictions. Top by Δscore:

Variant	Effect	Δscore
22:45345565:GACAC:G	acceptor_gain	1.0000
22:45345566:ACAC:A	acceptor_gain	1.0000
22:45345567:CAC:C	acceptor_gain	1.0000
22:45345567:CACC:C	acceptor_gain	1.0000
22:45345568:AC:A	acceptor_gain	1.0000
22:45345569:CC:C	acceptor_gain	1.0000
22:45345569:CCTG:C	acceptor_loss	1.0000
22:45345570:C:CC	acceptor_gain	1.0000
22:45345570:CTGG:C	acceptor_loss	1.0000
22:45358691:CATTA:C	donor_loss	1.0000
22:45358692:ATTAC:A	donor_loss	1.0000
22:45358693:TTACC:T	donor_loss	1.0000
22:45358694:TACCT:T	donor_loss	1.0000
22:45358695:ACCTT:A	donor_loss	1.0000
22:45358791:CCCAT:C	acceptor_gain	1.0000
22:45358792:CCAT:C	acceptor_gain	1.0000
22:45358792:CCATC:C	acceptor_gain	1.0000
22:45358793:CAT:C	acceptor_gain	1.0000
22:45358793:CATC:C	acceptor_gain	1.0000
22:45358794:AT:A	acceptor_gain	1.0000
22:45358794:ATCTG:A	acceptor_loss	1.0000
22:45358796:C:CC	acceptor_gain	1.0000
22:45358796:CTGAA:C	acceptor_loss	1.0000
22:45358797:T:A	acceptor_loss	1.0000
22:45358803:A:AC	acceptor_gain	1.0000
22:45358803:A:C	acceptor_gain	1.0000
22:45358805:A:AC	acceptor_gain	1.0000
22:45358805:A:C	acceptor_gain	1.0000
22:45361835:TTACC:T	donor_loss	1.0000
22:45361836:TACC:T	donor_loss	1.0000

AlphaMissense

8228 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000044848 (22:45398817 G>A), RS1000050334 (22:45407048 T>C), RS1000077293 (22:45399079 A>T), RS1000110235 (22:45410025 G>A), RS1000120097 (22:45410311 T>G), RS1000317860 (22:45360771 C>T), RS1000326377 (22:45405804 C>G), RS1000330626 (22:45343959 G>A,T), RS1000340348 (22:45344337 T>C), RS1000355886 (22:45390094 T>A), RS1000386655 (22:45412437 G>T), RS1000462868 (22:45398258 T>C), RS1000526782 (22:45404618 T>C), RS1000544622 (22:45364553 C>A), RS1000546049 (22:45353803 C>A)

Disease associations

OMIM: gene MIM:608685 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
gonadal dysgenesis	Limited	Autosomal dominant

Mondo (2): myoepithelial tumor (MONDO:0002380), gonadal dysgenesis (MONDO:0001967)

Orphanet (1): Rare genetic premature ovarian failure (Orphanet:485382)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005723_1	Peanut allergy (maternal genetic effects)	4.000000e-06
GCST008163_91	Height	6.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005939	parental genotype effect measurement
EFO:0007017	peanut allergy measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D006059	Gonadal Dysgenesis	C12.050.351.875.253.309; C12.200.706.316.309; C12.800.316.309; C16.131.939.316.309; C19.391.119.309
D009208	Myoepithelioma	C04.557.435.585

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	increases methylation, decreases methylation	2
GSK-J4	decreases expression	1
CGP 52608	increases reaction, affects binding	1
Glyphosate	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Lead	decreases expression	1
Niclosamide	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases methylation	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2GN	Abcam HeLa SMC1B KO	Cancer cell line	Female

Clinical trials (associated diseases)

9 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00001221	PHASE2	COMPLETED	Effect of Biosynthetic Growth Hormone and/or Ethinyl Estradiol on Adult Height in Patients With Turner Syndrome
NCT00001253	PHASE2	COMPLETED	The Effects of Estrogen on Cognition in Girls With Turner Syndrome
NCT03600649	PHASE1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT04189406	Not specified	UNKNOWN	Turner Syndrome Minipuberty Study
NCT06687252	Not specified	COMPLETED	Retrospective Analysis of the Neonatal Management of Patients with an Antenatal Diagnosis of Genital Development Variation At the Hospital of Lyon
NCT05266196	PHASE1/PHASE2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	PHASE1/PHASE2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06625190	PHASE1/PHASE2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT06244420	Not specified	COMPLETED	Malignant Myoepithelioma of Bone and Soft Tissues: Diagnostic Imaging and Histology in Relation to Prognosis