Table 4. Other defects in downstream TCR signalling, cytoskeleton activation and immune synapse formation [3, 19, 21, 22].

Disease	OMIM	Gene	Inheritance	Phenotype
Wiskott-Aldrich syndrome	#301000	WAS	XL (LOF)	Onset: early childhood with the classic triad: – Thrombocytopenia (pathognomonic small mean platelet volume (< 5 fL)) – Recurrent severe infections (impetigo, cellulitis, skin abscesses, molluscum contagiosum; Herpesviruses, including herpes simplex and varicella-zoster virus, Epstein-Barr virus) – Eczema, often unresponsive to conventional treatment. – Early death may result from bleeding. – Autoimmunity and malignancy more common with increasing age. – Milder phenotype: X-linked thrombocytopenia without eczema or immunodeficiency.
WIP deficiency	#614493	WIPF1	AR (LOF)	– WAS-like presentation, but very early onset of a severe immunodeficiency
NCKAP1L deficiency (HEM-1 hematopoietic protein 1)	#618982	NCKAP1L	AR (LOF)	– Atopic disease and hyperinflammation, chronic hepatosplenomegaly, lymphadenopathy – Recurrent fever and upper respiratory tract infections, skin rashes, abscesses, ulcers, autoimmune manifestations and FTT
DOCK8 deficiency	#243700	DOCK8	AR (LOF)	– Extensive, disfiguring, concurrently occurring cutaneous viral infections, particularly HSV, human papillomavirus, molluscum contagiosum and varicella-zoster virus. – Invasive infections (wide spectrum of Gram-positive and Gram-negative bacteria, viruses and intracellular fungi, e.g., histoplasma capsulatum). – Mucocutaneous candidiasis and recurrent gastro-intestinal tract infections are common. – Severe and extensive food allergies. – High risk of developing malignancies, particularly lymphomas and squamous cell carcinomas.
CARMIL2 (RLTPR) deficiency	#618131	CARMIL2	AR (LOF)	– Onset early infancy; – Atopic and seborrheic dermatitis and psoriasis-like rashes. – Viral (EBV, CMV, and varicella), bacterial, mycobacterial and fungal infections – Early or very early onset inflammatory bowel disease (VEOIBD) – Autoimmune polyendocrinopathy syndrome (APS) – Characteristic feature is EBV-associated leiomyoma (<20% of cases)
STK4 deficiency	#614868	STK4	AR (LOF)	– Onset at school age – Infections (cutaneous viral infections, recurrent pneumonia, EBV-associated lymphoproliferation) – Autoimmune or inflammatory diseases and atopic dermatitis/atopy
TBX21 deficiency (T-bet, T-box transcription factor 21)	#619630	TBX21	AR (LOF)	– Mendelian susceptibility to mycobacterial disease (MSMD) – Persistent upper airway inflammation
Moesin-associated immunodeficiency (X-MAID)	#300988	MSN	XLR (LOF)	– Skin manifestations, mainly eczema, molluscum contagiosum and increased susceptibility to bacterial and viral infections and VEOIBD

XL = X linked; LOF = loss of function; AD = autosomal dominant; AR = autosomal recessive; XLR = X-linked recessive; WAS = Wiscott-Aldrich syndrome; FTT = failure to thrive; HSV = Herpes simplex virus; EBV = Ebstein-Barr virus; CMV = cytomegalovirus; VEOIBD = very early onset inflammatory bowel disease.