RAD21

Summary

RAD21 (RAD21 cohesin complex component, HGNC:9811) is a protein-coding gene on chromosome 8q24.11, encoding Double-strand-break repair protein rad21 homolog (O60216). As a member of the cohesin complex, involved in sister chromatid cohesion from the time of DNA replication in S phase to their segregation in mitosis, a function that is essential for proper chromosome segregation, post-replicative DNA repair, and the prevention of inappropriate…. It is a common-essential gene (DepMap: required in 99.5% of cancer cell lines) and haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene is highly similar to the gene product of Schizosaccharomyces pombe rad21, a gene involved in the repair of DNA double-strand breaks, as well as in chromatid cohesion during mitosis. This protein is a nuclear phospho-protein, which becomes hyperphosphorylated in cell cycle M phase. The highly regulated association of this protein with mitotic chromatin specifically at the centromere region suggests its role in sister chromatid cohesion in mitotic cells.

Source: NCBI Gene 5885 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Cornelia de Lange syndrome (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 555 total — 40 pathogenic, 19 likely-pathogenic (top 6% of genes corpus-wide)
• Regional missense constraint (gnomAD): 2 of 5 regions constrained (≈34% of expected missense variation)
• GTEx eGene: eQTL in 27 tissues, sQTL in 3 (q < 0.05)
• Phenotypes (HPO): 160
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 2 cancer types (inferred from mutation patterns)
• Cancer dependency (DepMap): dependent in 99.5% of screened cell lines (common-essential)
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.34 (highly constrained)
• MANE Select transcript: NM_006265
• Interaction hub: 4,476 STRING partners (top 1% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9811
Approved symbol	RAD21
Name	RAD21 cohesin complex component
Location	8q24.11
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0078, hHR21, SCC1
Ensembl gene	ENSG00000164754
Ensembl biotype	protein_coding
OMIM	606462
Entrez	5885

Gene structure

Transcript identifiers

Ensembl transcripts: 43 — 24 protein_coding, 12 retained_intron, 6 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000297338

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 3, TSL 3: 3, TSL 4: 2

ENST00000297338, ENST00000517485, ENST00000517749, ENST00000518055, ENST00000519469, ENST00000519837, ENST00000520992, ENST00000522699, ENST00000523547, ENST00000523986, ENST00000685972, ENST00000686622, ENST00000687122, ENST00000687358, ENST00000687902, ENST00000688033, ENST00000689124, ENST00000689154, ENST00000689504, ENST00000690166, ENST00000690189, ENST00000900008, ENST00000900009, ENST00000900010, ENST00000900011, ENST00000927337, ENST00000927338, ENST00000927339, ENST00000927340, ENST00000927341, ENST00000958516, ENST00000958517, ENST00000958518, ENST00000958519, ENST00001006742, ENST00001011649, ENST00001011654, ENST00001074827, ENST00001074829, ENST00001109555, ENST00001129034, ENST00001129035, ENST00001135351

RefSeq mRNA: 1 — MANE Select: NM_006265 NM_006265

CCDS: CCDS6321

Canonical transcript exons

ENST00000297338 — 14 exons

Exon	Start	End
ENSE00001087180	116848946	116849029
ENSE00001087181	116857267	116857473
ENSE00001087182	116856646	116856771
ENSE00001087184	116851948	116852096
ENSE00001087186	116856166	116856288
ENSE00001087189	116850618	116850767
ENSE00001087190	116854245	116854468
ENSE00001087191	116852549	116852708
ENSE00001276365	116845934	116847691
ENSE00001356828	116874611	116874776
ENSE00003464321	116861841	116861940
ENSE00003464650	116866586	116866761
ENSE00003525419	116863130	116863259
ENSE00003579379	116858352	116858458

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 99.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 84.2621 / max 1535.8367, expressed in 1822 samples.

Highest expression (Bgee): ventricular zone, ganglionic eminence, superficial temporal artery, endometrium epithelium, epithelium of nasopharynx.

Genetic regulation across tissues (GTEx eQTL / sQTL)

RAD21 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 27 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 30 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	4.9e-26	-0.49	8:116876671:T:A
Nerve Tibial	eqtl	1.4e-21	-0.17	8:116885085:C:T
Skin Sun Exposed Lower leg	eqtl	4.5e-14	-0.12	8:116896606:T:TC
Artery Tibial	eqtl	1.1e-13	-0.14	8:116885085:C:T
Skin Not Sun Exposed Suprapubic	eqtl	4.4e-13	-0.11	8:116846150:G:A
Muscle Skeletal	eqtl	3.0e-12	-0.19	8:116828792:T:A
Testis	sqtl	2.8e-11	+0.68	8:116882227:A:G
Breast Mammary Tissue	eqtl	9.9e-11	-0.14	8:116886972:A:G
Artery Aorta	eqtl	2.5e-10	-0.14	8:116885085:C:T
Pituitary	eqtl	1.4e-08	-0.21	8:116841534:G:C
Whole Blood	eqtl	2.0e-08	-0.09	8:116868416:C:T
Esophagus Mucosa	eqtl	2.1e-07	-0.08	8:116885085:C:T
Adipose Subcutaneous	eqtl	6.4e-07	-0.08	8:116885085:C:T
Cells Cultured fibroblasts	eqtl	1.0e-06	-0.08	8:116846367:C:CAT
Esophagus Muscularis	eqtl	2.6e-06	-0.10	8:116919448:T:C
Lung	eqtl	6.3e-06	-0.11	8:116885085:C:T
Colon Transverse	eqtl	1.4e-05	-0.11	8:116846367:C:CAT
Heart Atrial Appendage	eqtl	5.4e-05	-0.09	8:116846367:C:CAT
Heart Left Ventricle	eqtl	9.5e-05	-0.09	8:116891826:A:G
Testis	eqtl	2.6e-04	-0.11	8:116895581:G:A

FANTOM5 promoters

showing 10 of 14 alternative TSS:

Promoter ID	TPM avg	Samples expressed
94550	84.2621	1822
94543	5.2653	1378
94549	3.1339	1109
94542	0.7315	177
94547	0.2810	112
94545	0.2576	132
94546	0.1360	41
94544	0.1335	36
94548	0.0770	25
94535	0.0534	2

Top tissues by expression

showing 100 of 301 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.47	gold quality
ganglionic eminence	UBERON:0004023	99.04	gold quality
superficial temporal artery	UBERON:0001614	98.85	gold quality
endometrium epithelium	UBERON:0004811	98.81	gold quality
epithelium of nasopharynx	UBERON:0001951	98.79	gold quality
germinal epithelium of ovary	UBERON:0001304	98.76	gold quality
cerebellar vermis	UBERON:0004720	98.76	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.69	gold quality
subthalamic nucleus	UBERON:0001906	98.66	gold quality
substantia nigra pars compacta	UBERON:0001965	98.66	gold quality
embryo	UBERON:0000922	98.63	gold quality
trabecular bone tissue	UBERON:0002483	98.53	gold quality
inferior vagus X ganglion	UBERON:0005363	98.53	gold quality
seminal vesicle	UBERON:0000998	98.51	gold quality
superior vestibular nucleus	UBERON:0007227	98.47	gold quality
corpus callosum	UBERON:0002336	98.44	gold quality
adult organism	UBERON:0007023	98.44	gold quality
lower lobe of lung	UBERON:0008949	98.38	gold quality
pigmented layer of retina	UBERON:0001782	98.34	gold quality
retina	UBERON:0000966	98.31	gold quality
colonic epithelium	UBERON:0000397	98.29	gold quality
middle frontal gyrus	UBERON:0002702	98.20	gold quality
lateral globus pallidus	UBERON:0002476	98.19	gold quality
medulla oblongata	UBERON:0001896	98.16	gold quality
thymus	UBERON:0002370	98.15	gold quality
trigeminal ganglion	UBERON:0001675	98.13	gold quality
bone marrow	UBERON:0002371	98.11	gold quality
bone element	UBERON:0001474	98.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.10	gold quality
paraflocculus	UBERON:0005351	98.06	gold quality
caput epididymis	UBERON:0004358	97.99	gold quality
cortical plate	UBERON:0005343	97.99	gold quality
frontal pole	UBERON:0002795	97.98	gold quality
adrenal tissue	UBERON:0018303	97.95	gold quality
corpus epididymis	UBERON:0004359	97.93	gold quality
lymph node	UBERON:0000029	97.92	gold quality
pons	UBERON:0000988	97.92	gold quality
oocyte	CL:0000023	97.91	gold quality
parietal pleura	UBERON:0002400	97.90	gold quality
oral cavity	UBERON:0000167	97.85	gold quality
heart right ventricle	UBERON:0002080	97.85	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.82	gold quality
Brodmann (1909) area 10	UBERON:0013541	97.81	gold quality
ventral tegmental area	UBERON:0002691	97.76	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.75	gold quality
jejunum	UBERON:0002115	97.74	gold quality
choroid plexus epithelium	UBERON:0003911	97.74	gold quality
renal medulla	UBERON:0000362	97.73	gold quality
cauda epididymis	UBERON:0004360	97.73	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	97.69	gold quality
jejunal mucosa	UBERON:0000399	97.68	gold quality
penis	UBERON:0000989	97.68	gold quality
colonic mucosa	UBERON:0000317	97.66	gold quality
secondary oocyte	CL:0000655	97.65	gold quality
dorsal root ganglion	UBERON:0000044	97.62	gold quality
bone marrow cell	CL:0002092	97.60	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	97.60	gold quality
islet of Langerhans	UBERON:0000006	97.57	gold quality
visceral pleura	UBERON:0002401	97.57	gold quality
superior surface of tongue	UBERON:0007371	97.56	gold quality
urethra	UBERON:0000057	97.53	gold quality
pleura	UBERON:0000977	97.53	gold quality
mammary duct	UBERON:0001765	97.51	gold quality
synovial joint	UBERON:0002217	97.48	gold quality
pylorus	UBERON:0001166	97.47	gold quality
CA1 field of hippocampus	UBERON:0003881	97.43	gold quality
rectum	UBERON:0001052	97.41	gold quality
tonsil	UBERON:0002372	97.39	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.39	gold quality
caecum	UBERON:0001153	97.34	gold quality
midbrain	UBERON:0001891	97.33	gold quality
myocardium	UBERON:0002349	97.33	gold quality
cartilage tissue	UBERON:0002418	97.30	gold quality
calcaneal tendon	UBERON:0003701	97.30	gold quality
orbitofrontal cortex	UBERON:0004167	97.29	gold quality
epithelium of mammary gland	UBERON:0003244	97.28	gold quality
endometrium	UBERON:0001295	97.25	gold quality
skin of hip	UBERON:0001554	97.25	gold quality
substantia nigra	UBERON:0002038	97.25	gold quality
globus pallidus	UBERON:0001875	97.22	gold quality
spinal cord	UBERON:0002240	97.21	gold quality
pericardium	UBERON:0002407	97.21	gold quality
cardia of stomach	UBERON:0001162	97.20	gold quality
upper leg skin	UBERON:0004262	97.20	gold quality
thoracic mammary gland	UBERON:0005200	97.19	gold quality
mammary gland	UBERON:0001911	97.17	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.16	gold quality
parietal lobe	UBERON:0001872	97.15	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.15	gold quality
vermiform appendix	UBERON:0001154	97.12	gold quality
postcentral gyrus	UBERON:0002581	97.10	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.07	gold quality
urinary bladder	UBERON:0001255	97.02	gold quality
vastus lateralis	UBERON:0001379	97.00	gold quality
right lung	UBERON:0002167	97.00	gold quality
tongue	UBERON:0001723	96.97	gold quality
gingiva	UBERON:0001828	96.97	gold quality
placenta	UBERON:0001987	96.93	gold quality
medial globus pallidus	UBERON:0002477	96.93	gold quality
hypothalamus	UBERON:0001898	96.92	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	37.08
E-CURD-122	yes	23.02
E-GEOD-125970	yes	16.52
E-MTAB-6678	yes	8.21
E-MTAB-10553	yes	7.48
E-GEOD-106540	no	818.43
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Thymus	tissue	151.4
Corpus callosum	tissue	140.5
Hippocampal formation	tissue	138.8
Thalamus	tissue	135.3
Superior colliculi	tissue	128.7
Midbrain	tissue	126.3
Cerebral cortex	tissue	124.1	high
Motor cortex	tissue	124.1
Prefrontal cortex	tissue	115.8
Bone marrow	tissue	115.5	high
Retrosplenial cortex	tissue	111.7
Amygdala	tissue	111.3
Hypothalamus	tissue	110.9
Pons	tissue	110.0
Entorhinal cortex	tissue	107.8
Retrosplenial and cingulate cortex	tissue	106.4
Cerebellum	tissue	105.6	high
Insular cortex	tissue	104.1
Occipital cortex	tissue	103.8
Somatosensory cortex	tissue	102.7
Tonsil	tissue	102.2	high
Lymph node	tissue	101.7	high
Septum	tissue	97.2
Substantia nigra	tissue	97.0
Temporal cortex	tissue	95.6
Periaqueductal gray	tissue	94.6
Medulla oblongata	tissue	93.3
Putamen	tissue	92.1
Olfactory bulb	tissue	90.2
Ventral forebrain	tissue	89.6
Spinal cord	tissue	87.8
Tongue	tissue	86.9
Retina	tissue	84.9
Heart muscle	tissue	80.8	medium
Nucleus accumbens	tissue	77.5
Locus coeruleus	tissue	77.1
Placenta	tissue	76.3	high
Frontal cortex	tissue	75.2
Caudate putamen	tissue	73.7
Parathyroid gland	tissue	73.5	high
Testis	tissue	73.4	high
Basal ganglia	tissue	72.0	high
Adrenal gland	tissue	70.7	high
Rectum	tissue	69.6	high
Thyroid gland	tissue	69.3	high
Hippocampus	tissue	68.1	high
Skeletal muscle	tissue	66.7	high
Adipose tissue	tissue	65.2	high
Choroid plexus	tissue	64.9
Colon	tissue	62.9	high
Ovary	tissue	62.2	high
Appendix	tissue	62.1	high
Kidney	tissue	61.7	high
Esophagus	tissue	61.3	high
Spleen	tissue	60.8	high
Postcentral gyrus	tissue	60.1
Breast	tissue	59.7	high
Liver	tissue	58.1	low
Lung	tissue	56.1	high
Seminal vesicle	tissue	55.8	high

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — White matter (140.5), Subiculum (138.8), Corpus callosum, genu (white matter) (131.6), Parieto-temporal junction (white matter) (126.2), Cerebellar white matter (122.8).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets:

Target	Regulation
APOB	Repression
RUNX1	Repression

Upstream regulators (CollecTRI, top): CTCF, ESR1, MYC, NR5A1, TFAP2A, TFAP2C

miRNA regulators (miRDB)

Targeting RAD21 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 153 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-433-3P	99.98	69.37	1203
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.341, missense Z 3.65 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000297338 splits into 5 regions with different missense tolerance; 2 are missense-constrained (≈34% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
8:116,847,503–116,847,645	34 / 59.9	0.57	no
8:116,847,646–116,852,659	225 / 218.3	1.03	no
8:116,852,660–116,856,197	42 / 117.2	0.36	yes (p 3.7e-12)
8:116,856,198–116,861,863	165 / 229.6	0.72	no
8:116,861,864–116,866,729	27 / 144.1	0.19	yes (p 1.8e-22)
ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map
DepMap (CRISPR cell-line fitness): dependent in 99.5% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): KLE (-2.844), NMC-G1 (-2.453), NCI-H226 (-2.367), RERF-GC-1B (-2.358), JM1 (-2.267), VCaP (-2.244), K-562 (-2.222), KP-N-YN (-2.217), ONCO-DG-1 (-2.204), KU812 (-2.2), NCI-H1092 (-2.191), TUHR10TKB (-2.174), SK-N-BE(2) (-2.16), SNU-449 (-2.125), IMR-32 (-2.109).

Literature-anchored findings (GeneRIF, showing 40)

• Caspase proteolysis of the cohesin component RAD21 promotes apoptosis (PMID:11875078)
• RAD21 subunit of the cohesin complex directly interacts with ATPase subunit SNF2; mapping of RAD21, SNF2 and Mi2 binding sites reveals specific association of these three proteins with DNA elements containing Alu sequences (PMID:12198550)
• Scc1 is essential for the association of kinetochores with microtubules. (PMID:12200439)
• plays a role in apoptosis, and its cleavage during apoptosis may act as a nuclear signal to initiate cytoplasmic events involved in the apoptotic pathway (PMID:12417729)
• RAD21 shows increased expression in clinical prostate carcinomas and is also amplified in 30-40% of xenografts and hormone-refractory tumors. (PMID:14603436)
• Phosphorylation of SA2 is essential for cohesin dissociation during prophase and prometaphase, but is not required for cohesin cleavage by separase. (PMID:15737063)
• RAD21 suppression enhances the antitumor activity of chemotherapeutic agents acting via induction of DNA damage (PMID:15767545)
• The RAD21 gene was closely related to the invasion and metastasis of cancer cells. (PMID:16416296)
• As compared to the telomerase group, the alternative lengthening of telomeres group presents higher expression of hRad21, thinner tumor invasion depth, and higher survival rate. (PMID:18197499)
• These data argue that the regulation of the IL-3 and the GM-CSF promoters depends on the positions of their enhancers relative to the conserved CTCF/cohesin-binding sites. (PMID:19158269)
• The depletion of either CTCF or RAD21 disrupts the chromatin loop structure, together with significant changes in the APO expression. (PMID:19322193)
• Ectopic expression of Rad21 repressed CTCF-regulated transcription of KSHV lytic genes. (PMID:19369356)
• hRAD21 was significantly differently expressed in cells maintaining telomere length through a telomerase-independent mechanism, termed the alternative lengthening of telomeres (ALT). (PMID:20364118)
• Rad21 protein depletion causes centrosome defects in interphase and prophase of mitosis. (PMID:20404533)
• Rad21 protein are cleaved by separase are required for the localization of Rad21 to the centrosome. (PMID:20404544)
• RAD21 expression confers poor prognosis and resistance to chemotherapy in high grade luminal, basal and HER2 breast cancers. (PMID:21255398)
• Rad21 cleavage by calpain-1 promotes separation of chromosome arms, which coincides with a calcium-induced partial loss of cohesin at several chromosomal loci. (PMID:21876002)
• RAD21 expression is associated with a poorer prognosis in BRCA2, but not in BRCA1 breast cancers. (PMID:22537934)
• RAD21 mutations cause a human cohesinopathy (PMID:22633399)
• show that the Smc5/6 subunit Mms21 sumoylates multiple lysines of the cohesin subunit Scc1 (PMID:22751501)
• ASURA specifically binds to chromatin when Scc1 is associated with chromatin. (PMID:23548868)
• Rad21 binds to SA proteins through two SA-binding motifs on Rad21. (PMID:23874961)
• -RAD21 and EIF3H, both on chromosome 8q23, CHRAC1 on chromosome 8q24.3 and TANC2 on chromosome 17q23-were confirmed to be driver genes regulating the proliferation/survival of clonogenic breast cancer cells (PMID:24148822)
• This study reports the first intragenic deletion and frameshift mutations identified in RAD21 in two patients presenting with atypical Cornelia de Lange syndrome. (PMID:24378232)
• CTCF and Rad21 act as host cell restriction factors for Kaposi’s sarcoma-associated herpesvirus (KSHV) lytic replication by modulating viral gene transcription. (PMID:24415941)
• RAD21 expression in CRC is associated with aggressive disease especially in KRAS mutant tumours and resistance to chemoradiotherapy. (PMID:24548858)
• Cross-sectional deep-sequencing analysis for clonal hierarchy demonstrated STAG2, SMC3, and RAD21 mutations to be ancestral in 18%, 18%, and 47% of cases, respectively, and each expanded to clonal dominance concordant with disease transformation (PMID:25006131)
• Studied the role of looping in large-scale (supra Mb) folding of human chromosomes by knocking down the gene that codes for CTCF and the one coding for Rad21, an essential subunit of cohesin. (PMID:25299688)
• cohesin’s proposed DNA exit gate is formed by interactions between Scc1 and the coiled-coil region of Smc3. (PMID:25414306)
• Elevated RAD21 expression tracks with reactivation of L1 expression in human sporadic colorectal cancer. (PMID:25464844)
• Some patients with chronic intestinal pseudo-obstruction carry mutations in RAD21 that disrupt the ability of its product to regulate genes such as RUNX1 and APOB. (PMID:25575569)
• found well-positioned CTCF and RAD21 peaks approximately 60-80 bp upstream of the TSS in the unidirectional genes. The peak heights were related to the amount of antisense transcription. Results provide insights into the distribution of histone modifications at promoters and suggest a novel role of CTCF and cohesin as regulators of transcriptional direction. (PMID:25881024)
• Reduced RAD21 destabilizes high-level gene amplification by disrupting pre-replication complex bindings in human cancers with chromosomal instability. (PMID:26420833)
• Data indicate that RAD21 plays an important role in cellular senescence breast cancer cells, mainly through RB1 pathway activation via c-Myc downregulation. (PMID:26529363)
• This study together with previous reports suggests incomplete penetrance associated with RAD21 variants and these individuals may therefore be underdiagnosed. (PMID:27882533)
• With tissue microarrays of hepatocellular carcinoma (HCC) patients, we determined the prognostic values of the core genes in the network and found that RAD21, CDK1, and HDAC2 expression levels were negatively associated with overall survival for HCC patients. (PMID:28434945)
• evidence for a possible pathogenetic role of RAD21 promoter methylation in the development of chronic lymphocytic leukemia. (PMID:29587287)
• depletion of Rad21 in a Pds5-deficient background rescues the phenotype observed upon Pds5 depletion alone. These findings support a model where loss of either component of the cohesin releasin complex perturbs cohesin dynamics on replication forks, hindering fork progression and promoting MRE11-dependent fork slowing (PMID:29917110)
• A subset of PGP9.5- and HuC/D-IR neuronal cell bodies and nerve fibers in the myenteric plexus of human and mouse small intestine also displayed cytoplasmic RAD21 (PMID:30069982)
• We demonstrate that infection of hepatoma cells with HCV leads to up regulation of the expression of the RAD21 cohesin subunit and changes cohesin residency on the chromatin. (PMID:30698808)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rad21a	ENSDARG00000006092
danio_rerio	rad21b	ENSDARG00000035655
mus_musculus	Rad21	ENSMUSG00000022314
rattus_norvegicus	Rad21	ENSRNOG00000004420
drosophila_melanogaster	vtd	FBGN0260987
caenorhabditis_elegans		WBGENE00004737

Paralogs (2): REC8 (ENSG00000100918), RAD21L1 (ENSG00000244588)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:108016) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 9 distinct phenotype terms.

Mouse phenotype (MP)	Records
reduced male fertility	1
abnormal T cell differentiation	1
abnormal CD4-positive, alpha beta T cell morphology	1
decreased double-positive T cell number	1
abnormal female meiosis	1
abnormal CD4-positive, alpha-beta T cell physiology	1
decreased CD4-positive, alpha-beta T cell number	1
decreased CD8-positive, alpha-beta T cell number	1
prenatal lethality, incomplete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q3SWX9	98.3%	Diamond
Ailuropoda melanoleuca	D2HSB3	84.9%	Diamond
Xenopus laevis	O93310	83.6%	Diamond
Schizosaccharomyces pombe 972h-	P30776	49.3%	Diamond
Arabidopsis thaliana	Q9FQ19	49.3%	Diamond
Saccharomyces cerevisiae S288C	Q12158	35.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
AARD	protein-coding	441376
RAD21-AS1	ncRNA	644660
UTP23	protein-coding	84294
MIR3610	ncRNA	100500914
SLC30A8	protein-coding	169026
EIF3H	protein-coding	8667

Protein

Protein identifiers

Double-strand-break repair protein rad21 homolog — O60216 (reviewed: O60216)

Alternative names: Nuclear matrix protein 1, SCC1 homolog

All UniProt accessions (7): A0A8I5KWV3, E5RFV8, E5RG18, E5RIN7, E5RJK5, E5RJW1, O60216

UniProt curated annotations — full annotation on UniProt →

Function. As a member of the cohesin complex, involved in sister chromatid cohesion from the time of DNA replication in S phase to their segregation in mitosis, a function that is essential for proper chromosome segregation, post-replicative DNA repair, and the prevention of inappropriate recombination between repetitive regions. The cohesin complex may also play a role in spindle pole assembly during mitosis. In interphase, cohesins may function in the control of gene expression by binding to numerous sites within the genome. May control RUNX1 gene expression. Binds to and represses APOB gene promoter. May play a role in embryonic gut development, possibly through the regulation of enteric neuron development. May promote apoptosis.

Subunit / interactions. Component of the cohesin complex, which consists of an SMC1A/B and SMC3 heterodimer core and 2 non-Smc subunits RAD21 and STAG1/SA1, STAG2/SA2 or STAG3/SA3. Interacts (via C-terminus) with SMC1A and (via N-terminus) with SMC3; these interactions are direct. The cohesin complex interacts with NUMA1. The cohesin complex also interacts with CDCA5, PDS5A and PDS5B; this interaction might regulate the ability of the cohesin complex to mediate sister chromatid cohesion. The interaction with PDS5B is direct and is stimulated by STAG1/SA1. 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. The cohesin complex interacts with DDX11/ChIR1. Directly interacts with WAPL; this interaction is stimulated by STAG1/SA1. Interacts with the ISWI chromatin remodeling complex component SMARCA5/SNF2h; the interaction is direct. Interacts with the NuRD complex component CHD4; the interaction is direct.

Subcellular location. Nucleus. Nucleus matrix. Chromosome. Centromere. Cytoplasm. Cytoskeleton. Spindle pole Cytoplasm. Cytosol.

Tissue specificity. Expressed in the gut (at protein level).

Post-translational modifications. Cleaved by separase/ESPL1 at the onset of anaphase; this cleavage is required for sister chromatid separation and cytokinesis. Cleaved by caspase-3/CASP3 or caspase-7/CASP7 at the beginning of apoptosis. Phosphorylated; becomes hyperphosphorylated in M phase of cell cycle. The large dissociation of cohesin from chromosome arms during prophase may be partly due to its phosphorylation by PLK1.

Disease relevance. Cornelia de Lange syndrome 4 with or without midline brain defects (CDLS4) [MIM:614701] A form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. It is characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation, hirsutism, gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies. The disease is caused by variants affecting the gene represented in this entry. Mungan syndrome (MGS) [MIM:611376] An autosomal recessive disease characterized by visceral neuromyopathy, intestinal dysmotility and chronic intestinal pseudoobstruction, megaduodenum, long-segment Barrett esophagus, and a variety of cardiac valve or septal defects such as membranous ventricular septal defect, pulmonary and tricuspid valve regurgitation. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The C-terminal part associates with the ATPase head of SMC1A, while the N-terminal part binds to the ATPase head of SMC3.

Similarity. Belongs to the rad21 family.

RefSeq proteins (1): NP_006256* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006909	Rad21/Rec8_C_eu	Domain
IPR006910	Rad21_Rec8_N	Domain
IPR023093	ScpA-like_C	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR039781	Rad21/Rec8-like	Family
IPR049589	NXP1_M-like	Domain

Pfam: PF04824, PF04825

UniProt features (66 total): helix 19, modified residue 8, region of interest 7, mutagenesis site 7, sequence variant 5, compositionally biased region 4, strand 4, site 3, cross-link 3, turn 3, chain 2, sequence conflict 1

Structure

Experimental structures (PDB)

showing 30 of 37 structures by resolution:

PDB	Title	Method	Resolution (Å)
8ROE	Human cohesin SMC1A-HD(shortCC-EQ)/RAD21-C complex - ADP-bound conformation	X-RAY DIFFRACTION	1.36
8ROD	Human cohesin SMC1A-HD(shortCC-EQ)/RAD21-C complex - Open/closed P-loop conformation	X-RAY DIFFRACTION	1.5
8ROF	Human cohesin SMC1A-HD(shortCC-EQ)/RAD21-C complex - ADP-Mg-bound conformation	X-RAY DIFFRACTION	1.65
8RO9	Human cohesin SMC1A-HD(longCC-EQ)/RAD21-C complex - Open/closed P-loop conformation	X-RAY DIFFRACTION	1.77
8ROC	Human cohesin SMC1A-HD(shortCC-EQ)/RAD21-C complex - Apo closed P-loop conformation	X-RAY DIFFRACTION	1.85
8RO8	Human cohesin SMC1A-HD(longCC-EQ)/RAD21-C complex - Apo closed P-loop conformation	X-RAY DIFFRACTION	1.9
8ROG	Human cohesin SMC1A-HD(shortCC-EQ)/RAD21-C complex - ATPgS-Mg-bound conformation	X-RAY DIFFRACTION	1.94
8RO7	Human cohesin SMC1A-HD(longCC)/RAD21-C complex - Open/closed P-loop conformation	X-RAY DIFFRACTION	2.09
8RO6	Human cohesin SMC1A-HD(longCC)/RAD21-C complex - Apo closed P-loop conformation	X-RAY DIFFRACTION	2.2
8ROK	Human cohesin SMC3-HD(EQ)/RAD21-N complex - ATP-Mg-bound conformation - Form 1	X-RAY DIFFRACTION	2.25
6RRC	Crystal structure of the N-terminal region of human cohesin subunit STAG1 in complex with …	X-RAY DIFFRACTION	2.37
8ROA	Human cohesin SMC1A-HD(longCC-EQ)/RAD21-C complex - ADP-bound conformation	X-RAY DIFFRACTION	2.44
8ROI	Human cohesin SMC3-HD(EQ)/RAD21-N complex - ADP-bound conformation	X-RAY DIFFRACTION	2.45
8ROB	Human cohesin SMC1A-HD(longCC-EQ)/RAD21-C complex - ATPgS-Mg-bound conformation	X-RAY DIFFRACTION	2.5
8ROH	Human cohesin SMC3-HD(EQ)/RAD21-N complex - Apo conformation	X-RAY DIFFRACTION	2.6
6QNX	Structure of the SA2/SCC1/CTCF complex	X-RAY DIFFRACTION	2.7
9HN0	Cryo-EM structure of human separase bound to SCC1 (310-550 aa)	ELECTRON MICROSCOPY	2.8
4PJW	crystal structure of human Stromal Antigen 2 (SA2) in complex with Sister Chromatid …	X-RAY DIFFRACTION	2.85
9HMV	Cryo-EM structure of SA2-SCC1 complex at 2.9 angstrom	ELECTRON MICROSCOPY	2.9
9HN4	Cryo-EM structure of human separase bound to phosphorylated SCC1 (310-550 aa)	ELECTRON MICROSCOPY	2.93
4PK7	crystal structure of human Stromal Antigen 2 (SA2) in complex with Sister Chromatid …	X-RAY DIFFRACTION	2.95
9HN5	Cryo-EM structure of human separase bound to phosphorylated SCC1 (100-320 aa)	ELECTRON MICROSCOPY	2.96
8ROJ	Human cohesin SMC3-HD/RAD21-N complex - ADP-Mg-bound conformation	X-RAY DIFFRACTION	3
4PJU	crystal structure of human Stromal Antigen 2 (SA2) in complex with Sister Chromatid …	X-RAY DIFFRACTION	3.05
9HX9	Structure of the SA2/SCC1/MCM3 complex	X-RAY DIFFRACTION	3.07
9EP3	Structure of the SA2/SCC1/WAPL complex	X-RAY DIFFRACTION	3.08
8ROL	Human cohesin SMC3-HD(EQ)/RAD21-N complex - ATP-Mg-bound conformation - Form 2	X-RAY DIFFRACTION	3.11
6RRK	Crystal structure of the central region of human cohesin subunit STAG1 in complex with …	X-RAY DIFFRACTION	3.17
7ZJS	Structural basis of centromeric cohesion protection by SGO1	X-RAY DIFFRACTION	3.24
9HMS	Cryo-EM structure of human separase bound to SCC1 (310-550 aa) and SA2	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60216-F1	61.49	0.20

Human Protein Atlas

Protein class: Predicted intracellular proteins, Cancer-related genes, Mutated cancer genes, Mutational cancer driver genes, Disease related genes, Human disease related genes, Congenital malformations, Other congenital malformations, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH supported · IF enhanced

Functional residue map

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

Catalytic / active sites (3)

Position	Role
172–173	cleavage; by espl1
279–280	cleavage; by caspase-3 or caspase-7
450–451	cleavage; by espl1

Post-translational modifications (11)

Type	Positions
Phosphoserine	46, 153, 175, 249, 454, 545
Phosphothreonine	394, 623
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	48, 216, 418

Mutagenesis-validated functional residues (7)

Position	Phenotype
1–126	abolishes interaction with smc1.
126–282	abolishes binding to smarca5.
172	abolishes first cleavage by espl1, no effect on nuclear localization.
276–280	loss of cleavage by caspase-3 or caspase-7.
279	loss of cleavage by caspase-3 or caspase-7.
282	no effect on cleavage by caspase-3 or caspase-7.
450	abolishes second cleavage by espl1, no effect on nuclear localization.

Function

Pathways and Gene Ontology

Reactome pathways

6 curated (TAS) of 24; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

24 pathways:

ID	Pathway	Evidence
R-HSA-2470946	Cohesin Loading onto Chromatin	curated
R-HSA-2468052	Establishment of Sister Chromatid Cohesion	curated
R-HSA-9018519	Estrogen-dependent gene expression	curated
R-HSA-2500257	Resolution of Sister Chromatid Cohesion	curated
R-HSA-3108214	SUMOylation of DNA damage response and repair proteins	curated
R-HSA-2467813	Separation of Sister Chromatids	curated
R-HSA-1640170	Cell Cycle	—
R-HSA-69278	Cell Cycle, Mitotic	—
R-HSA-8939211	ESR-mediated signaling	—
R-HSA-68886	M Phase	—
R-HSA-1500620	Meiosis	—
R-HSA-1221632	Meiotic synapsis	electronic
R-HSA-392499	Metabolism of proteins	—
R-HSA-68882	Mitotic Anaphase	—
R-HSA-2555396	Mitotic Metaphase and Anaphase	—
R-HSA-68877	Mitotic Prometaphase	—
R-HSA-68884	Mitotic Telophase/Cytokinesis	—
R-HSA-597592	Post-translational protein modification	—
R-HSA-1474165	Reproduction	—
R-HSA-69242	S Phase	—
R-HSA-3108232	SUMO E3 ligases SUMOylate target proteins	—
R-HSA-2990846	SUMOylation	—
R-HSA-162582	Signal Transduction	—
R-HSA-9006931	Signaling by Nuclear Receptors	—

MSigDB gene sets: 742 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, MORF_MTA1, GOBP_CHROMOSOME_ORGANIZATION, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, FREAC2_01, MORF_MBD4, TGCGCANK_UNKNOWN, REACTOME_MEIOTIC_SYNAPSIS, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GEORGES_CELL_CYCLE_MIR192_TARGETS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MORF_RAD21

GO Biological Process (26): response to hypoxia (GO:0001666), double-strand break repair (GO:0006302), DNA recombination (GO:0006310), DNA-templated transcription (GO:0006351), regulation of transcription by RNA polymerase II (GO:0006357), apoptotic process (GO:0006915), chromosome segregation (GO:0007059), sister chromatid cohesion (GO:0007062), reciprocal meiotic recombination (GO:0007131), negative regulation of G2/M transition of mitotic cell cycle (GO:0010972), negative regulation of interleukin-1 beta production (GO:0032691), negative regulation of tumor necrosis factor production (GO:0032720), positive regulation of interleukin-10 production (GO:0032733), establishment of mitotic sister chromatid cohesion (GO:0034087), establishment of meiotic sister chromatid cohesion (GO:0034089), negative regulation of glial cell apoptotic process (GO:0034351), negative regulation of neuron apoptotic process (GO:0043524), negative regulation of mitotic metaphase/anaphase transition (GO:0045841), positive regulation of sister chromatid cohesion (GO:0045876), cell division (GO:0051301), protein localization to chromatin (GO:0071168), replication-born double-strand break repair via sister chromatid exchange (GO:1990414), DNA repair (GO:0006281), DNA damage response (GO:0006974), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629)

GO Molecular Function (6): cis-regulatory region sequence-specific DNA binding (GO:0000987), chromatin binding (GO:0003682), lncRNA binding (GO:0106222), DNA-binding transcription factor binding (GO:0140297), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (12): chromosome, centromeric region (GO:0000775), chromatin (GO:0000785), condensed nuclear chromosome (GO:0000794), spindle pole (GO:0000922), nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), cytosol (GO:0005829), cohesin complex (GO:0008278), membrane (GO:0016020), nuclear matrix (GO:0016363), meiotic cohesin complex (GO:0030893)

Reactome top-level categories

15 top-level categories:

Category	Pathways
M Phase	3
Meiosis	1
Mitotic Anaphase	1
S Phase	1
Mitotic Telophase/Cytokinesis	1
Mitotic Prometaphase	1
SUMO E3 ligases SUMOylate target proteins	1
ESR-mediated signaling	1
Reproduction	1
Cell Cycle	1
Post-translational protein modification	1
SUMOylation	1
Metabolism of proteins	1
Mitotic Metaphase and Anaphase	1
Cell Cycle, Mitotic	1

GO top-level categories

showing 60 of 67 GO namespaces:

Category	Terms
cellular anatomical structure	6
cell cycle process	2
negative regulation of mitotic cell cycle phase transition	2
establishment of sister chromatid cohesion	2
negative regulation of apoptotic process	2
binding	2
chromosome	2
nuclear lumen	2
response to stress	1
response to decreased oxygen levels	1
DNA repair	1
DNA metabolic process	1
gene expression	1
RNA biosynthetic process	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
chromosome organization	1
meiosis I	1
reciprocal homologous recombination	1
meiotic cell cycle process	1
G2/M transition of mitotic cell cycle	1
regulation of G2/M transition of mitotic cell cycle	1
negative regulation of cell cycle G2/M phase transition	1
interleukin-1 beta production	1
regulation of interleukin-1 beta production	1
negative regulation of interleukin-1 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
negative regulation of tumor necrosis factor superfamily cytokine production	1
positive regulation of cytokine production	1
interleukin-10 production	1
regulation of interleukin-10 production	1
mitotic cell cycle	1
mitotic sister chromatid cohesion	1
mitotic cell cycle process	1
meiotic sister chromatid cohesion	1
glial cell apoptotic process	1
regulation of glial cell apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
metaphase/anaphase transition of mitotic cell cycle	1
regulation of mitotic metaphase/anaphase transition	1
negative regulation of mitotic nuclear division	1
negative regulation of metaphase/anaphase transition of cell cycle	1
negative regulation of mitotic sister chromatid separation	1
sister chromatid cohesion	1
regulation of sister chromatid cohesion	1
positive regulation of cell cycle process	1
positive regulation of chromosome organization	1
cellular process	1
transcription cis-regulatory region binding	1
RNA binding	1
transcription factor binding	1
nucleic acid binding	1
chromosomal region	1
nuclear chromosome	1
condensed chromosome	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 44 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
positive regulation of sister chromatid cohesion	BP	mutant phenotype
protein localization to chromatin	BP	mutant phenotype
regulation of transcription by RNA polymerase II	BP	direct assay
cohesin complex	CC	direct assay
membrane	CC	high-throughput assay
nuclear matrix	CC	direct assay
nucleoplasm	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 4,476 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAD21	SMC3	Q9UQE7	993
RAD21	ESPL1	Q14674	982
RAD21	SMC1A	Q14683	971
RAD21	NIPBL	Q6KC79	970
RAD21	STAG2	Q8N3U4	966
RAD21	STAG1	Q8WVM7	958
RAD21	PDS5A	Q29RF7	953
RAD21	WAPL	Q7Z5K2	937
RAD21	SMC4	Q9NTJ3	884
RAD21	CTCF	P49711	875
RAD21	ESCO1	Q5FWF5	872
RAD21	SGO1	Q5FBB7	851
RAD21	ESCO2	Q56NI9	826
RAD21	SGO2	Q562F6	807
RAD21	CHTF18	Q8WVB6	806

IntAct

Human interaction partners of RAD21 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 38 partners by confidence:

Partner	Interaction type	MIscore	Records
STAG2	association	0.970	15
SMC3	physical association	0.960	10
SMC1A	physical association	0.930	15
STAG1	association	0.930	7
WAPL	colocalization	0.910	14
PDS5B	association	0.860	6
PDS5A	association	0.860	3
SGO1	physical association	0.740	6
SSU72	physical association	0.670	7
FHL3	physical association	0.670	4
CDCA5	association	0.640	3
ESPL1	direct interaction	0.620	3
CPNE5	association	0.530	1
NIPBL	physical association	0.490	2
AIRE	physical association	0.400	1
CTCF	physical association	0.400	1
HAND2	physical association	0.400	1
ARL5B	association	0.350	2
REC8	association	0.350	2
BRCA2	association	0.350	1
CITED1	association	0.350	1
CPNE9	association	0.350	1
GOLGA7	association	0.350	1
HSD17B1	association	0.350	1
KLHL20	association	0.350	1
RABIF	association	0.350	1
SMC2	association	0.350	1
FBXW7	proximity	0.270	4
SMARCA4	proximity	0.270	4
SPOP	proximity	0.270	4

BioGRID (616 interactions; top human partners by supporting records in a sample of 600 records): SMC3 (Co-fractionation; 28 records), SMC1A (Co-fractionation; 24 records), STAG2 (Co-fractionation; 21 records), STAG1 (Co-fractionation; 18 records), WAPAL (Affinity Capture-MS; 13 records), CDCA5 (Affinity Capture-MS; 9 records), PDS5A (Affinity Capture-MS; 9 records), PDS5B (Affinity Capture-Western; 9 records), USP13 (Affinity Capture-MS; 5 records), CCAR2 (Affinity Capture-MS; 3 records), CDC34 (Affinity Capture-MS; 3 records), FHL3 (Two-hybrid; 3 records), HIST1H4A (Affinity Capture-MS; 3 records), MCM7 (Co-fractionation; 3 records), NSMCE2 (Biochemical Activity; 3 records)

SIGNOR signaling

showing 12 of 13 signaling interactions:

A	Effect	B	Mechanism
PRSS21	up-regulates	RAD21	cleavage
RAD21	“down-regulates quantity by repression”	RUNX1	“transcriptional regulation”
RAD21	“down-regulates quantity”	APOB	“transcriptional regulation”
STAG2	“up-regulates quantity by stabilization”	RAD21	binding
RAD21	“down-regulates activity”	GATA2	relocalization
RAD21	“down-regulates activity”	RUNX1	relocalization
RAD21	“down-regulates activity”	ERG	relocalization
PLK1	“down-regulates quantity by destabilization”	RAD21	dephosphorylation
ESPL1	“down-regulates quantity by destabilization”	RAD21	cleavage
RAD21	“up-regulates activity”	DNA_repair
RAD21	“form complex”	“Cohesin complex”	binding
CC2D1A	“up-regulates activity”	RAD21	binding

Protein complexes (CORUM) (6)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

6 complexes by size:

Complex	Subunits	Members
★ SNF2h-cohesin-NuRD complex	16	MBD2, MTA2, RBBP7, SMARCA5, MTA1, RBBP4, HDAC2, RAD21, SMC3, STAG1, STAG2, BAZ1A, HDAC1, MBD3, SMC1A, CHD3
Sororin-cohesin complex	6	SMC1A, SMC3, CDCA5, PDS5A, PDS5B, RAD21
Cohesin-SA1 complex	4	SMC3, STAG1, RAD21, SMC1A
Cohesin-SA2 complex	4	SMC3, STAG2, RAD21, SMC1A
DDX11-RAD21-SMC1A-SMC3 complex	4	SMC1A, SMC3, DDX11, RAD21
NIPBL-RAD21-SMC1A complex	3	NIPBL, RAD21, SMC1A

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 38 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Meiosis	5	46.0×	2e-06
S Phase	6	35.1×	5e-07
Reproduction	5	30.7×	1e-05
Resolution of Sister Chromatid Cohesion	10	27.9×	1e-10
Meiotic synapsis	5	22.7×	6e-05
Mitotic Metaphase and Anaphase	7	21.9×	7e-07
Mitotic Anaphase	7	21.9×	7e-07
Separation of Sister Chromatids	11	21.6×	1e-10

GO biological processes:

GO term	Partners	Fold	FDR
mitotic sister chromatid cohesion	6	177.4×	3e-10
sister chromatid cohesion	6	121.0×	1e-09
cell division	11	13.4×	5e-08
positive regulation of ERK1 and ERK2 cascade	5	11.2×	3e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 2 cancer types — AML, LUSC.

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for RAD21: 555 ClinVar records (59 pathogenic / likely pathogenic); 2 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	40
Likely pathogenic	19
Uncertain significance	213
Likely benign	170
Benign	50

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 59 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
802434	NM_006265.3(RAD21):c.144+1G>A	Pathogenic	criteria provided, multiple submitters, no conflicts	2
985588	NM_006265.3(RAD21):c.1222G>T (p.Gly408Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1805433	NM_006265.3(RAD21):c.1635del (p.Gly547fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2631614	NM_006265.3(RAD21):c.160C>T (p.Arg54Trp)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
998067	NM_006265.3(RAD21):c.9C>A (p.Tyr3Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
560415	NM_006265.3(RAD21):c.1864G>A (p.Ala622Thr)	Pathogenic	criteria provided, single submitter	2
864835	NM_006265.3(RAD21):c.589C>T (p.Gln197Ter)	Pathogenic	criteria provided, single submitter	2
864836	NM_006265.3(RAD21):c.1217_1224del (p.Lys406fs)	Pathogenic	criteria provided, single submitter	2
1185049	NM_006265.3(RAD21):c.943_946del (p.Glu315fs)	Pathogenic	criteria provided, single submitter	2
211993	NM_006265.3(RAD21):c.56_62del (p.Leu19fs)	Pathogenic	criteria provided, single submitter	1
211994	NM_006265.3(RAD21):c.579dup (p.Glu194fs)	Pathogenic	criteria provided, single submitter	1
211995	NM_006265.3(RAD21):c.592_593dup (p.Ser198fs)	Pathogenic	criteria provided, single submitter	1
280268	NM_006265.3(RAD21):c.578T>A (p.Leu193Ter)	Pathogenic	criteria provided, single submitter	1
418706	NM_006265.3(RAD21):c.1651del (p.Gln551fs)	Pathogenic	criteria provided, single submitter	1
436481	NM_006265.3(RAD21):c.181_182dup (p.Gly62fs)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore RAD21’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 28 predictions of 1,123):

Position(s)	Effect	Δscore	Sites
8:116847692–116847693	acceptor_loss	1.0000	2
8:116850768–116850769	acceptor_loss	1.0000	5
8:116850769	acceptor_gain	1.0000
8:116850776–116850777	acceptor_gain	1.0000	2
8:116851946–116851947	donor_loss	1.0000	5
8:116852097	acceptor_loss	1.0000
8:116852101–116852103	acceptor_gain	1.0000	2
8:116852109–116852111	acceptor_gain	1.0000	3
8:116852511	donor_gain	1.0000
8:116852709–116852710	acceptor_loss	1.0000	6

AlphaMissense

2,123 missense substitutions predicted likely pathogenic (of 4,235 scored), across 406 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M361	9	0.996	1.000
M87	9	0.949	0.999
M51	9	0.926	1.000
H22	8	1.000	1.000
H58	8	1.000	1.000
D77	8	1.000	1.000
D327	8	1.000	1.000
F89	8	0.999	1.000
F2	8	0.998	1.000
D95	8	0.998	1.000
D346	8	0.997	0.999
D352	8	0.995	0.998
F117	8	0.994	1.000
F304	8	0.994	1.000
H31	8	0.991	0.999
F114	8	0.987	1.000
D24	8	0.986	1.000
D116	8	0.986	0.998
F33	8	0.985	1.000
F597	8	0.984	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.87e-05
Kidney Chromophobe (TCGA)	unfavorable	3.58e-05
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.000622
Lung Adenocarcinoma (TCGA)	unfavorable	0.000923

Disease associations

OMIM: gene MIM:606462 | disease phenotypes: MIM:614701, MIM:122470, MIM:611376

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
Cornelia de Lange syndrome 4	Definitive	Autosomal dominant	4
Cornelia de Lange syndrome	Definitive	Autosomal dominant	2
Mungan syndrome	Strong	Autosomal recessive	2

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
Cornelia de Lange syndrome	Definitive	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (15 panels, 11 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

15 panels:

Panel	Rating
Cerebral malformation	green
Clefting	green
DDG2P	green
Fetal anomalies	green
Haematological malignancies cancer susceptibility	green
Holoprosencephaly	green
Hypotonic infant	green
IUGR and IGF abnormalities	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Severe microcephaly	green
Paediatric disorders	amber
Paediatric pseudo-obstruction syndrome	amber
Radial dysplasia	amber
Skeletal dysplasia	amber

Mondo (5): Cornelia de Lange syndrome 4 (MONDO:0013864), Cornelia de Lange syndrome (MONDO:0016033), Cornelia de Lange syndrome 1 (MONDO:0007387), Mungan syndrome (MONDO:0012657), acute megakaryoblastic leukemia in down syndrome (MONDO:0020526)

Orphanet (2): Cornelia de Lange syndrome (Orphanet:199), Acute megakaryoblastic leukemia in children with Down syndrome (Orphanet:99887)

HPO phenotypes

showing 60 of 160 phenotypes (HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000059	Hypoplastic labia majora
HP:0000076	Vesicoureteral reflux
HP:0000083	Renal insufficiency
HP:0000089	Renal hypoplasia
HP:0000130	Abnormality of the uterus
HP:0000164	Abnormality of the dentition
HP:0000174	Abnormal palate morphology
HP:0000175	Cleft palate
HP:0000176	Submucous cleft hard palate
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000220	Velopharyngeal insufficiency
HP:0000233	Thin vermilion border
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000294	Low anterior hairline
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000381	Stapes ankylosis
HP:0000400	Macrotia
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000411	Protruding ear
HP:0000413	Atresia of the external auditory canal
HP:0000414	Bulbous nose
HP:0000431	Wide nasal bridge
HP:0000453	Choanal atresia
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000482	Microcornea
HP:0000486	Strabismus
HP:0000498	Blepharitis
HP:0000501	Glaucoma
HP:0000508	Ptosis
HP:0000518	Cataract
HP:0000527	Long eyelashes
HP:0000545	Myopia
HP:0000574	Thick eyebrow
HP:0000582	Upslanted palpebral fissure
HP:0000601	Hypotelorism
HP:0000639	Nystagmus
HP:0000664	Synophrys
HP:0000667	Phthisis bulbi
HP:0000684	Delayed eruption of teeth
HP:0000687	Widely spaced teeth
HP:0000717	Autism
HP:0000722	Compulsive behaviors
HP:0000739	Anxiety
HP:0000767	Pectus excavatum
HP:0000768	Pectus carinatum

GWAS associations

2 associations:

Study	Trait	p-value
GCST005863_11	Menopause (age at onset)	2e-8
GCST005863_29	Menopause (age at onset)	3e-7

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004704	age at menopause

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
C548078	Mungan Syndrome *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

57 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases expression, decreases expression	3
Particulate Matter	increases abundance, affects expression, decreases expression	3
bisphenol A	decreases expression, affects cotreatment, increases expression	2
trichostatin A	affects cotreatment, decreases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
echimidine	increases metabolic processing, decreases expression	1
TAK-243	decreases sumoylation	1
pradimicin-IRD	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
lasiocarpine	decreases expression, increases metabolic processing	1
triphenyl phosphate	affects expression	1
riddelliine	decreases expression, increases metabolic processing	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
afimoxifene	affects response to substance	1
sodium arsenite	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	increases expression, affects cotreatment	1
coumarin	decreases phosphorylation	1
beta-methylcholine	affects expression	1
deguelin	increases expression	1
nickel acetate	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
torcetrapib	increases expression	1
ICG 001	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	decreases expression	1

Cellosaurus cell lines

32 cell lines: 29 cancer cell line, 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_0393	LN-229	Cancer cell line	Female
CVCL_0589	Kasumi-1	Cancer cell line	Male
CVCL_1632	P31/FUJ	Cancer cell line	Male
CVCL_A5S0	SEES3-1V human RAD21, clone1	Embryonic stem cell	Male
CVCL_A5S1	SEES3-1V human RAD21, clone2	Embryonic stem cell	Male
CVCL_A5S2	SEES3-1V human RAD21, clone3	Embryonic stem cell	Male
CVCL_A602	CMY	Cancer cell line	Male
CVCL_A8V5	LN229/CD20	Cancer cell line	Female
CVCL_D2R8	LN229/mCCR3	Cancer cell line	Female
CVCL_D2RM	LN229/mCD39	Cancer cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 252 trials:

NCT	Phase	Status	Title
NCT05657860	Phase 4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	Phase 4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	Phase 4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	Phase 4	RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	Phase 3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT04381897	Phase 2	NOT_YET_RECRUITING	Use of N-Acetylcysteine in the Treatment of Repetitive and Self-Injurious Behaviors in Cornelia de Lange Syndrome
NCT02304302	Phase 2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	Phase 2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	Phase 2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	Phase 2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT01773278	Phase 2	UNKNOWN	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT05273320	Phase 1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	Phase 1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	Phase 1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	Phase 1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	Phase 1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT06789783	Phase 2/3	RECRUITING	Cornelia De Lange Syndrome: Assessing Positive Effects of Lithium Treatment
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT03113877	Not specified	TERMINATED	Evaluation of Autonomic Function in Individuals With Cornelia de Lange Syndrome (CdLS)
NCT04463316	Not specified	RECRUITING	GROWing Up With Rare GENEtic Syndromes
NCT05829668	Not specified	RECRUITING	Behavioral Assessment and Treatment of Problem Behavior in Children With Cornelia de Lange Syndrome
NCT03479476	Phase 2/3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	Phase 1/2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	Early Phase 1	TERMINATED	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders
NCT02862808	Not specified	COMPLETED	Molecular Diagnosis of Syndromic or Isolated Severe Intellectual Disability Using Whole Exome Sequencing : a Pilot Study
NCT02881333	Not specified	UNKNOWN	Various Type of Genetic Events in Patients With Intellectual Disability
NCT02889068	Not specified	COMPLETED	Targeted Next Generation Sequencing and Intellectual Disability
NCT02914951	Not specified	ENROLLING_BY_INVITATION	Cognitive-Behavioral Therapy for Irritability in Children With Autism Spectrum Disorder and Intellectual Disability
NCT02919826	Not specified	COMPLETED	Dialectical Behaviour Group Therapy for Adults With Intellectual Disabilities
NCT02934854	Not specified	WITHDRAWN	Biomarker for Creatine Deficiency Syndromes (BioCDS)
NCT03033797	Not specified	UNKNOWN	Augmentative and Alternative Communication in Games With Virtual Reality in Intellectual Disabilities
NCT03135236	Not specified	COMPLETED	Parents as the Primary Sexuality Educators for Their Young Adults With Down Syndrome
NCT03139760	Not specified	COMPLETED	POWERSforID: A Telehealth Weight Management System for Adults With Intellectual Disability
NCT03203226	Not specified	COMPLETED	The Feldenkrais Method for People With Intellectual Disability
NCT03212092	Not specified	COMPLETED	Reducing Aggression Among People With an Intellectual Disability
NCT03218462	Not specified	COMPLETED	Effect of Sensory Adapted Dental Environment on Dental Anxiety of Children With Intellectual and Developmental Disabilities
NCT03234231	Not specified	UNKNOWN	Supervised Brushing Programme for Intellectual Disabled Students