Table 2.

X chromosome genes that may drive the phenotypic impacts of variation in Xi copy number

Region	Gene symbol	Gene name	NPY gene symbol	ΔEX		Gene constraint (average % ranking)a	Disease associations
				LCL	Fib.		Phenotype	Inheritanceb	MIM #
NPX	KDM6A	lysine demethylase 6A	UTY	0.83	0.45	93.3	Kabuki syndrome	XLD	300867
	KDM5C	lysine demethylase 5C	KDM5D	0.73	0.58	90.3	Claes-Jensen syndrome	XLR	300534
	SMC1A	structural maintenance of chromosomes 1A	–	0.58	0.43	87.6	Cornelia de Lange syndrome; developmental and epileptic encephalopathy	XLD	300590, 301044
	ZFX	zinc finger protein X-linked	ZFY	0.45	0.47	83.0	–	–	–
	RBBP7	RB-binding protein 7, chromatin remodeling factor	–	0.01	0.29	82.5	–	–	–
	DDX3X	DEAD-box helicase 3 X-linked	DDX3Y	0.26	0.16	89.2	syndromic IDD,c Snijders Blok type	XLD, XLR	300958
	CDK16	Cyclin dependent kinase 16	–	0.09	0.24	83.8	–	–	–
	DLG3	discs large MAGUK scaffold protein 3	–	0.18	0.07	82.8	IDD	XLR	300580
	USP9X	ubiquitin-specific protease 9 X-linked	USP9Y	0.14	0.17	94.4	IDD	XLR, XLD	300919, 300968
	BCOR	BCL6 corepressor	–	0.12	0.01	91.1	oculofaciocardiodental syndrome	XLD	300166
PAR1	SLC25A6	solute carrier family 25 member 6	N/A	1.0	0.74	67.4	–	–	–
	SHOX	short stature homeobox	N/A	N/Ad	N/A	58.4	Leri-Weill dyschondrosteosis; Langer mesomelic dysplasia; short stature idiopathic familial	PD, PR	127300, 249700, 300582

^aGene constraint percentile ranking is calculated for NPX genes relative to all annotated NPX genes and for PAR1 genes relative to all PAR and autosomal genes.

^bXLD, X-linked dominant; XLR, X-linked recessive; PD, pseudoautosomal dominant; PR, pseudoautosomal recessive.

^cIDD, intellectual developmental disorder.

^dSHOX is not expressed in fibroblasts or LCLs but is included because its dosage has been conclusively linked to height in individuals with sex chromosome aneuploidy.